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Xue C, Lu M, Qin Y, Zhao X, Yang J, Yuan S, Wang Z, Cho N, Jiang C. Polygonati Rhizoma polysaccharide suppresses microglial activation and promotes functional recovery of spinal cord via improving intestinal microbiota. Int J Biol Macromol 2025:143934. [PMID: 40345303 DOI: 10.1016/j.ijbiomac.2025.143934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 04/16/2025] [Accepted: 05/03/2025] [Indexed: 05/11/2025]
Abstract
Spinal cord injury (SCI) can disrupt the gut microbiome and metabolites, impacting prognosis, substantially impairing quality of life, and leading to high socioeconomic costs (Jing et al., 2021). Recent studies indicate that plant polysaccharides exhibit antimicrobial, anti-inflammatory, and immune-enhancing properties, contributing positively to various neurological disorders; however, their role in SCI remains uncertain (Hou et al., 2020 [2]; Aswini et al., 2021 [3]; Dou et al., 2019 [4]). Polygonati Rhizoma polysaccharide (PRP) has shown anti-inflammatory and immunoregulatory effects, but its role in SCI remains unexplored. This study investigated whether PRP facilitates functional recovery after SCI by modulating the gut microbiota and SCFA levels. PRP was administered to SCI mice, and motor function was assessed using DeepLabCut-based behavioral analysis. Histological evaluations were performed with H&E, Nissl, and immunofluorescence staining. Microglial activation and inflammation were analyzed by Western blot and immunofluorescence. Gut microbiota composition and SCFAs were examined through 16S rRNA sequencing and targeted metabolite profiling. PRP treatment significantly improved motor function, reduced microglial activation, and attenuated neuroinflammation. These effects were associated with restoration of microbial diversity and elevated butyrate levels. This study highlights the role of the gut-brain axis in neural regeneration and suggests PRP as a promising therapeutic candidate for SCI.
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Affiliation(s)
- Chang Xue
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea; Jiuhuashan Polygonati Rhizoma Research Institute, Chizhou 247100, China
| | - Mengqi Lu
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Jiuhuashan Polygonati Rhizoma Research Institute, Chizhou 247100, China.
| | - Yuwen Qin
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Jiuhuashan Polygonati Rhizoma Research Institute, Chizhou 247100, China.
| | - Xiaoli Zhao
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Jinfeng Yang
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Shutong Yuan
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Zhouguang Wang
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
| | - Namki Cho
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.
| | - Chengxi Jiang
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Jiuhuashan Polygonati Rhizoma Research Institute, Chizhou 247100, China.
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Liu CQ, Yang J, Ren HF, Liao GN, Yin Z, Gao SL, Du QJ, Yuan XZ, Ullah H, Li K. Diversity of intestinal microbiota and inflammatory cytokines after severe trauma. Sci Rep 2025; 15:7955. [PMID: 40055423 PMCID: PMC11889259 DOI: 10.1038/s41598-025-92212-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 02/26/2025] [Indexed: 03/17/2025] Open
Abstract
Accumulating evidence has reported that the intestinal microbiota could play important roles in the occurrence and progression of severe trauma. However, the hypothesized potential targeted intestinal microbiota to mediate and regulate the levels of inflammatory cytokines and promote rapid recovery of body after severe trauma remains unclear. This study was aimed to explore the changes and correlation of intestinal microbiota and inflammatory cytokines in rats with severe crush and fracture trauma. The controlled laboratory study design was used, and a crush and fracture severe trauma rat model was established. 16S rRNA high-throughput gene sequencing and ELISA were used to analyze the changes in intestinal microbiota and inflammatory cytokines within one week after trauma. The correlation between intestinal microbiota and inflammatory cytokines was also analyzed. Loss of overall diversity and expansion of intestinal microbiota in the rats due to severe trauma was observed. Specifically, there was a significant increase in the abundance of Muribaculaceae [LDA (Linear Discriminant Analysis)-value = 4.814, P = 0.014] after severe trauma, while Prevotella (LDA-value = 5.235, P = 0.020) and Alloprevotella (LDA-value = 4.443, P = 0.015) were slightly lower in the trauma group than in the control group. The levels of inflammatory cytokines (IL-1α, IL-6, IL-8 and TNF-α) in the trauma group decreased from the first day to the third day and continued to increase until one week after the trauma. Prevotellaceae_UCG_001 was correlated with TNF-a (R = 0.411, P = 0.033); Lactobacillus was negatively correlated with IL-6 (R = - 0.434, P = 0.024) and IL-1α (R = - 0.419, P = 0.030) and positively correlated with IL-8 (R = 0.391, P = 0.045); and Lachnospiraceae_NK4A136_group (R = - 0.559, P = 0.027) and Muribaculaceae (R = - 0.568, P = 0.024) were negatively correlated with IL-8. Severe trauma shows stress-like activities by negatively modulating intestinal microbiota and affecting certain inflammatory cytokines contributing to host health, which implies that the regulation of potentially targeted intestinal microbiota, and further mediating and maintaining the homeostasis of inflammatory cytokines, is expected to promote the accelerating recovery of the body after severe trauma.
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Affiliation(s)
- Chang-Qing Liu
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Jie Yang
- Department of Colorectal Tumour Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Hong-Fei Ren
- Department of Gastroenterology of West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Guang-Neng Liao
- Animal Experiment Center of West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Zhe Yin
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Shi-Lin Gao
- Department of Colorectal Tumour Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Qiu-Jing Du
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Xing-Zhu Yuan
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Hanif Ullah
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
| | - Ka Li
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
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Zhang D, Peng R, Yang D. A preliminary study on the changes of fecal short chain fatty acids in patients with traumatic spinal cord injury in the chronic phase. Spinal Cord Ser Cases 2025; 11:3. [PMID: 40000601 PMCID: PMC11861907 DOI: 10.1038/s41394-025-00698-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 11/13/2024] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
STUDY DESIGN Cross-sectional explorative observational study. SETTING The China Rehabilitation Research Center is one of the centers for spinal cord injury in China, and this study investigates the Chinese part of spinal cord injury. OBJECTIVE To observe the changes of fecal short-chain fatty acids (SCFA) in patients with traumatic spinal cord injury (TSCI) compared with normal controls. METHODS Thirty-eight patients with TSCI who were hospitalized in Beijing Boai Hospital of China Rehabilitation Research Center from April, 2017 to October, 2018 were recruited. Basic data such as age, gender, neurological level, etiology, and defecation method were recorded, and neurogenic bowel dysfunction score (NBD) was assessed. Twenty-one healthy subjects from the staffs of Beijing Bo'ai Hospital were recruited as the control group. Fresh stool samples were collected and gas chromatography-mass spectrometry (GC-MS) was used to determine the contents of caproic acid, isovaleric acid, isobutyric acid, valeric acid, butyric acid, propionic acid and acetic acid in feces of TSCI patients and controls. The Mann-Whitney U test was used to compare SCFA levels between the two groups. RESULTS Compared with healthy controls, the levels of isovaleric acid and isobutyric acid in the feces of TSCI patients increased, while the levels of butyric acid and acetic acid decreased, and the differences were statistically significant (P < 0.05). CONCLUSION The fecal content of propionic acid and butyric acid decreased while that of isobutyric acid and isoamyl acid increased in patients with chronic TSCI.
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Affiliation(s)
- Dejian Zhang
- Department of Emergency Medicine, Beijing Bo'Ai Hospital, China Rehabilitation Research Center, 100068, Beijing, China
- School of Rehabilitation, Capital Medical University, 10069, Beijing, China
| | - Run Peng
- School of Rehabilitation, Capital Medical University, 10069, Beijing, China
- Department of Spinal and Neural Functional Reconstruction, Beijing Bo'Ai Hospital, China Rehabilitation Research Center, 100068, Beijing, China
| | - Degang Yang
- School of Rehabilitation, Capital Medical University, 10069, Beijing, China.
- Department of Spinal and Neural Functional Reconstruction, Beijing Bo'Ai Hospital, China Rehabilitation Research Center, 100068, Beijing, China.
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Ju C, Liu R, Ma Y, Dong H, Xu R, Hu H, Hao D. Targeted microbiota dysbiosis repair: An important approach to health management after spinal cord injury. Ageing Res Rev 2025; 104:102648. [PMID: 39725357 DOI: 10.1016/j.arr.2024.102648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 12/18/2024] [Accepted: 12/21/2024] [Indexed: 12/28/2024]
Abstract
Current research primarily focuses on the pathological mechanisms of spinal cord injury (SCI), seeking to promote spinal cord repair and restore motorial and sensory functions by elucidating mechanisms of cell death or axonal regeneration. However, SCI is almost irreversible, and patients often struggle to regain mobility or self-care abilities after injuries. Consequently, there has been significant interest in modulating systemic symptoms following SCI to improve patients' quality of life. Neuron axonal disconnection and substantial apoptotic events following SCI result in signal transmission loss, profoundly impacting various organ and systems, including the gastrointestinal tract. Dysbiosis can lead to severe bowel dysfunction in patients, substantially lowering their quality of life and significantly reducing life expectancy of them. Therefore, researches focusing on the restoration of the gut microbiota hold promise for potential therapeutic strategies aimed at rehabilitation after SCI. In this paper, we explore the regulatory roles that dietary fiber, short-chain fatty acids (SCFAs), probiotics, and microbiota transplantation play in patients with SCI, summarize the potential mechanisms of post-SCI dysbiosis, and discuss possible strategies to enhance long-term survival of SCI patients. We aim to provide potential insights for future research aimed at ameliorating dysbiosis in SCI patients.
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Affiliation(s)
- Cheng Ju
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Youyidong Road, Xi'an, Shaanxi 710000, China; Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710000, China.
| | - Renfeng Liu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Youyidong Road, Xi'an, Shaanxi 710000, China; Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710000, China.
| | - Yanming Ma
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Youyidong Road, Xi'an, Shaanxi 710000, China; Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710000, China.
| | - Hui Dong
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Youyidong Road, Xi'an, Shaanxi 710000, China; Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710000, China.
| | - Ruiqing Xu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Youyidong Road, Xi'an, Shaanxi 710000, China; Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710000, China.
| | - Huimin Hu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Youyidong Road, Xi'an, Shaanxi 710000, China; Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710000, China.
| | - Dingjun Hao
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Youyidong Road, Xi'an, Shaanxi 710000, China; Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710000, China.
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Agarwal C, Koerner IP. Crosstalk between brain and the gastrointestinal system. BRAIN AND ORGAN COMMUNICATION 2025:195-213. [DOI: 10.1016/b978-0-443-22268-9.00011-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Pagan-Rivera LH, Ocasio-Rivera SE, Godoy-Vitorino F, Miranda JD. Spinal cord injury: pathophysiology, possible treatments and the role of the gut microbiota. Front Microbiol 2024; 15:1490855. [PMID: 39744391 PMCID: PMC11688470 DOI: 10.3389/fmicb.2024.1490855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 12/05/2024] [Indexed: 01/11/2025] Open
Abstract
Spinal cord injury (SCI) is a devastating pathological state causing motor, sensory, and autonomic dysfunction. To date, SCI remains without viable treatment for its patients. After the injury, molecular events centered at the lesion epicenter create a non-permissive environment for cell survival and regeneration. This newly hostile setting is characterized by necrosis, inflammation, demyelination, axotomy, apoptosis, and gliosis, among other events that limit locomotor recovery. This review provides an overview of the pathophysiology of SCI, highlighting the potential role of the gut microbiota in modulating the inflammatory response and influencing neurological recovery following trauma to the spinal cord. Emphasis on the bidirectional communication between the gut and central nervous system, known as the gut-brain axis is given. After trauma, the gut-brain/spinal cord axis promotes the production of pro-inflammatory metabolites that provide a non-permissive environment for cell survival and locomotor recovery. Therefore, any possible pharmacological treatment, including antibiotics and painkillers, must consider their effects on microbiome dysbiosis to promote cell survival, regeneration, and behavioral improvement. Overall, this review provides valuable insights into the pathophysiology of SCI and the evolving understanding of the role of the gut microbiota in SCI, with implications for future research and clinical practice.
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Affiliation(s)
- Luis H. Pagan-Rivera
- Physiology Department, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Samuel E. Ocasio-Rivera
- Physiology Department, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Filipa Godoy-Vitorino
- Microbiology and Medical Zoology Department, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Jorge D. Miranda
- Physiology Department, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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Goodus MT, Alfredo AN, Carson KE, Dey P, Pukos N, Schwab JM, Popovich PG, Gao J, Mo X, Bruno RS, McTigue DM. Spinal cord injury-induced metabolic impairment and steatohepatitis develops in non-obese rats and is exacerbated by premorbid obesity. Exp Neurol 2024; 379:114847. [PMID: 38852834 PMCID: PMC11874686 DOI: 10.1016/j.expneurol.2024.114847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 05/27/2024] [Accepted: 06/06/2024] [Indexed: 06/11/2024]
Abstract
Impaired sensorimotor functions are prominent complications of spinal cord injury (SCI). A clinically important but less obvious consequence is development of metabolic syndrome (MetS), including increased adiposity, hyperglycemia/insulin resistance, and hyperlipidemia. MetS predisposes SCI individuals to earlier and more severe diabetes and cardiovascular disease compared to the general population, which trigger life-threatening complications (e.g., stroke, myocardial infarcts). Although each comorbidity is known to be a risk factor for diabetes and other health problems in obese individuals, their relative contribution or perceived importance in propagating systemic pathology after SCI has received less attention. This could be explained by an incomplete understanding of MetS promoted by SCI compared with that from the canonical trigger diet-induced obesity (DIO). Thus, here we compared metabolic-related outcomes after SCI in lean rats to those of uninjured rats with DIO. Surprisingly, SCI-induced MetS features were equal to or greater than those in obese uninjured rats, including insulin resistance, endotoxemia, hyperlipidemia, liver inflammation and steatosis. Considering the endemic nature of obesity, we also evaluated the effect of premorbid obesity in rats receiving SCI; the combination of DIO + SCI exacerbated MetS and liver pathology compared to either alone, suggesting that obese individuals that sustain a SCI are especially vulnerable to metabolic dysfunction. Notably, premorbid obesity also exacerbated intraspinal lesion pathology and worsened locomotor recovery after SCI. Overall, these results highlight that normal metabolic function requires intact spinal circuitry and that SCI is not just a sensory-motor disorder, but also has significant metabolic consequences.
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Affiliation(s)
- Matthew T Goodus
- The Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Anthony N Alfredo
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Neuroscience Graduate Program, The Ohio State University, Columbus, OH 43210, USA
| | - Kaitlin E Carson
- The Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India
| | - Nicole Pukos
- The Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Neuroscience Graduate Program, The Ohio State University, Columbus, OH 43210, USA
| | - Jan M Schwab
- The Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Neurology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Phillip G Popovich
- The Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Jie Gao
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Xiaokui Mo
- Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Richard S Bruno
- Human Nutrition Program, College of Education and Human Ecology, The Ohio State University, Columbus, OH, USA
| | - Dana M McTigue
- The Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
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Valido E, Capossela S, Glisic M, Hertig-Godeschalk A, Bertolo A, Stucki G, Flueck JL, Stoyanov J. Gut microbiome and inflammation among athletes in wheelchair in a crossover randomized pilot trial of probiotic and prebiotic interventions. Sci Rep 2024; 14:12838. [PMID: 38834634 PMCID: PMC11150429 DOI: 10.1038/s41598-024-63163-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/26/2024] [Indexed: 06/06/2024] Open
Abstract
Disorders related to gut health are a significant cause of morbidity among athletes in wheelchair. This pilot feasibility trial aims to investigate whether probiotics compared to prebiotics can improve inflammatory status and gut microbiome composition in elite athletes in wheelchair. We conducted a 12-week, randomized, cross-over controlled trial involving 14 elite Swiss athletes in wheelchair. Participants were given a multispecies-multistrain probiotic or prebiotic (oat bran) daily for 4 weeks (Clinical trials.gov NCT04659408 09/12/2020). This was followed by a 4-week washout and then crossed over. Thirty inflammatory markers were assessed using bead-based multiplex immunoassays (LegendPlex) from serum samples. The gut microbiome was characterized via 16S rRNA sequencing of stool DNA samples. Statistical analyses were conducted using linear mixed-effect models (LMM). At baseline, most athletes (10/14) exhibited low levels of inflammation which associated with higher gut microbiome alpha diversity indices compared to those with high inflammation levels. The use of probiotic had higher decrease in 25 (83%) inflammatory markers measured compared to prebiotic use. Probiotic has the potential in lowering inflammation status and improving the gut microbiome diversity. The future trial should focus on having sufficient sample sizes, population with higher inflammation status, longer intervention exposure and use of differential abundance analysis.
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Affiliation(s)
- Ezra Valido
- Swiss Paraplegic Research, 6207, Nottwil, Switzerland.
| | | | - Marija Glisic
- Swiss Paraplegic Research, 6207, Nottwil, Switzerland
- Institute of Social and Preventive Medicine (ISPM), University of Bern, 3012, Bern, Switzerland
| | | | - Alessandro Bertolo
- Swiss Paraplegic Research, 6207, Nottwil, Switzerland
- Department of Orthopedic Surgery, University of Bern, Bern Inselspital, 3012, Bern, Switzerland
| | - Gerold Stucki
- Swiss Paraplegic Research, 6207, Nottwil, Switzerland
- Faculty of Health Sciences and Medicine, University of Lucerne, 6003, Lucerne, Switzerland
| | - Joelle Leonie Flueck
- Institute of Sports Medicine, Swiss Paraplegic Centre, 6207, Nottwil, Switzerland
| | - Jivko Stoyanov
- Swiss Paraplegic Research, 6207, Nottwil, Switzerland
- Institute of Social and Preventive Medicine (ISPM), University of Bern, 3012, Bern, Switzerland
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9
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Shen CL, Santos JM, Elmassry MM, Bhakta V, Driver Z, Ji G, Yakhnitsa V, Kiritoshi T, Lovett J, Hamood AN, Sang S, Neugebauer V. Ginger Polyphenols Reverse Molecular Signature of Amygdala Neuroimmune Signaling and Modulate Microbiome in Male Rats with Neuropathic Pain: Evidence for Microbiota-Gut-Brain Axis. Antioxidants (Basel) 2024; 13:502. [PMID: 38790607 PMCID: PMC11118883 DOI: 10.3390/antiox13050502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 04/13/2024] [Accepted: 04/17/2024] [Indexed: 05/26/2024] Open
Abstract
Emerging evidence shows that the gut microbiota plays an important role in neuropathic pain (NP) via the gut-brain axis. Male rats were divided into sham, spinal nerve ligation (SNL), SNL + 200 mg GEG/kg BW (GEG200), and SNL + 600 mg GEG/kg BW (GEG600) for 5 weeks. The dosages of 200 and 600 mg GEG/kg BW for rats correspond to 45 g and 135 g raw ginger for human daily consumption, respectively. Both GEG groups mitigated SNL-induced NP behavior. GEG-supplemented animals had a decreased abundance of Rikenella, Muribaculaceae, Clostridia UCG-014, Mucispirillum schaedleri, RF39, Acetatifactor, and Clostridia UCG-009, while they had an increased abundance of Flavonifactor, Hungatella, Anaerofustis stercorihominis, and Clostridium innocuum group. Relative to sham rats, Fos and Gadd45g genes were upregulated, while Igf1, Ccl2, Hadc2, Rtn4rl1, Nfkb2, Gpr84, Pik3cg, and Abcc8 genes were downregulated in SNL rats. Compared to the SNL group, the GEG200 group and GEG600 group had increases/decreases in 16 (10/6) genes and 11 (1/10) genes, respectively. GEG downregulated Fos and Gadd45g genes and upregulated Hdac2 genes in the amygdala. In summary, GEG alleviates NP by modulating the gut microbiome and reversing a molecular neuroimmune signature.
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Affiliation(s)
- Chwan-Li Shen
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (J.M.S.)
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA;
- Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Julianna Maria Santos
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (J.M.S.)
| | - Moamen M. Elmassry
- Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA
| | - Viren Bhakta
- Department of Biology, Texas Tech University, Lubbock, TX 79401, USA
| | - Zarek Driver
- Department of Biochemistry, Texas Tech University, Lubbock, TX 79401, USA
| | - Guangchen Ji
- Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (G.J.); (V.Y.); (T.K.)
| | - Vadim Yakhnitsa
- Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (G.J.); (V.Y.); (T.K.)
| | - Takaki Kiritoshi
- Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (G.J.); (V.Y.); (T.K.)
| | - Jacob Lovett
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (J.M.S.)
| | - Abdul Naji Hamood
- Department of Microbiology and Infectious Disease, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA;
| | - Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post Harvest Technologies, North Carolina A&T State University, North Carolina Research Campus, Kannapolis, NC 28081, USA;
| | - Volker Neugebauer
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA;
- Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (G.J.); (V.Y.); (T.K.)
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Cui Y, Liu J, Lei X, Liu S, Chen H, Wei Z, Li H, Yang Y, Zheng C, Li Z. Dual-directional regulation of spinal cord injury and the gut microbiota. Neural Regen Res 2024; 19:548-556. [PMID: 37721283 PMCID: PMC10581592 DOI: 10.4103/1673-5374.380881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 04/17/2023] [Accepted: 06/05/2023] [Indexed: 09/19/2023] Open
Abstract
There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis. The spinal cord is a vital important part of the central nervous system; however, the underlying association between spinal cord injury and gut interactions remains unknown. Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis. Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury. This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury. Our research identified three key points. First, the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury. Second, following spinal cord injury, weakened intestinal peristalsis, prolonged intestinal transport time, and immune dysfunction of the intestine caused by abnormal autonomic nerve function, as well as frequent antibiotic treatment, may induce gut dysbiosis. Third, the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury; cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system. Fecal microbiota transplantation, probiotics, dietary interventions, and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota. Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.
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Affiliation(s)
- Yinjie Cui
- Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
- School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jingyi Liu
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiao Lei
- International Cooperation and Exchange Office, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Shuwen Liu
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Haixia Chen
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhijian Wei
- International Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - Hongru Li
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuan Yang
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chenguang Zheng
- Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
| | - Zhongzheng Li
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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11
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Li S, Chen T, Zhou Y, Li X. Palmitic acid and trans-4-hydroxy-3-methoxycinnamate, the active ingredients of Yaobishu formula, reduce inflammation and pain by regulating gut microbiota and metabolic changes after lumbar disc herniation to activate autophagy and the Wnt/β-catenin pathway. Biochim Biophys Acta Mol Basis Dis 2024; 1870:166972. [PMID: 38016505 DOI: 10.1016/j.bbadis.2023.166972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 11/17/2023] [Accepted: 11/22/2023] [Indexed: 11/30/2023]
Abstract
The imbalance in gut microbiota triggers an inflammatory response that spreads from the gut to the discs and is associated with lumbar disc herniation (LDH). In this study, we investigated the mechanism of palmitic acid (PA) and trans-4-hydroxy-3-methoxycinnamic acid (THMC) on microbiota, metabolic homeostasis, and autophagy after LDH. The LDH rat model was established by puncturing the exposed intervertebral disc. 16S rDNA was used to assess the gut microbiome composition. The microbial metabolites were analyzed by UPLC-MS. The mechanism of PA and THMC in LDH was explored by fecal microbiota transplantation (FMT). We found that Yaobishu, PA, THMC, and the positive control drug Celebrex attenuated intervertebral disc damage in LDH rats and downregulated TRPV1, IL-1β, and IL-18 expression. In addition, Yaobishu reduced Oscillospirales and Ruminococcaceae abundances after LDH. PA increased Bacilli's abundance while decreasing Negativicutes and Ruminococcaceae abundances. Metabolomics showed that Yaobishu increased 2-hexanone, methyl isobutyl ketone, 2-methylpentan-3-one, and nonadecanoic acid levels but decreased pantetheine and urocanate levels. PA and THMC reduced uridine and urocanate levels. Yaobishu, PA, and THMC activated autophagy and the Wnt/β-catenin pathway in LDH rats. Moreover, antibiotics abrogated these effects. FMT-PA and FMT-THMC activated autophagy and decreased IL-1β, IL-18, Wnt1, β-catenin, and TRPV1 expression. FMT-PA and FMT-THMC partially reversed the effects of 3-MA. Taken together, our data suggest that Yaobishu, PA, and THMC relieve inflammation and pain by remodeling the gut microbiota and restoring metabolic homeostasis after LDH to activate autophagy and the Wnt/β-catenin pathway, which provide a new therapeutic target for LDH in the clinic.
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Affiliation(s)
- ShuoQi Li
- Department of Orthopaedics, Hunan Provincial People's Hospital, Changsha, Hunan, 410001, China
| | - TieZhu Chen
- Department of Orthopaedics, Hunan Provincial People's Hospital, Changsha, Hunan, 410001, China
| | - YiZhao Zhou
- Department of Orthopaedics, Hunan Provincial People's Hospital, Changsha, Hunan, 410001, China
| | - XiaoSheng Li
- Department of Orthopaedics, Hunan Provincial People's Hospital, Changsha, Hunan, 410001, China.
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12
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DiSabato DJ, Marion CM, Mifflin KA, Alfredo AN, Rodgers KA, Kigerl KA, Popovich PG, McTigue DM. System failure: Systemic inflammation following spinal cord injury. Eur J Immunol 2024; 54:e2250274. [PMID: 37822141 PMCID: PMC10919103 DOI: 10.1002/eji.202250274] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 10/06/2023] [Accepted: 10/10/2023] [Indexed: 10/13/2023]
Abstract
Spinal cord injury (SCI) affects hundreds of thousands of people in the United States, and while some effects of the injury are broadly recognized (deficits to locomotion, fine motor control, and quality of life), the systemic consequences of SCI are less well-known. The spinal cord regulates systemic immunological and visceral functions; this control is often disrupted by the injury, resulting in viscera including the gut, spleen, liver, bone marrow, and kidneys experiencing local tissue inflammation and physiological dysfunction. The extent of pathology depends on the injury level, severity, and time post-injury. In this review, we describe immunological and metabolic consequences of SCI across several organs. Since infection and metabolic disorders are primary reasons for reduced lifespan after SCI, it is imperative that research continues to focus on these deleterious aspects of SCI to improve life span and quality of life for individuals with SCI.
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Affiliation(s)
- Damon J. DiSabato
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio, USA
| | - Christina M. Marion
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio, USA
| | - Katherine A. Mifflin
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio, USA
| | - Anthony N. Alfredo
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA
| | - Kyleigh A. Rodgers
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA
| | - Kristina A. Kigerl
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio, USA
| | - Phillip G. Popovich
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio, USA
| | - Dana M. McTigue
- Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio, USA
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13
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Guha L, Agnihotri TG, Jain A, Kumar H. Gut microbiota and traumatic central nervous system injuries: Insights into pathophysiology and therapeutic approaches. Life Sci 2023; 334:122193. [PMID: 37865177 DOI: 10.1016/j.lfs.2023.122193] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 10/12/2023] [Accepted: 10/18/2023] [Indexed: 10/23/2023]
Abstract
Traumatic brain injury and spinal cord injury are two distinct but fundamentally similar types of acute insults to the central nervous system (CNS) that often culminate in death or cognitive and motor impairment. Over the past decade, researchers have tapped into research to discover the potential role being played by gut bacteria in CNS. After an acute CNS injury, the altered composition of the gut microbiota disturbs the balance of the bidirectional gut-brain axis, aggravating secondary CNS injury, motor dysfunctions, and cognitive deficits, which worsens the patient's prognosis. Some of the well-known therapeutic interventions which can also be used as adjuvant therapy for alleviating CNS injuries include, the use of pro and prebiotics, fecal microbiota transplantation, and microbial engineering. In this review, we aim to discuss the importance of gut microbes in our nervous system, anatomy, and signaling pathways involved in regulating the gut-brain axis, the alteration of the gut microbiome in CNS injuries, and the therapeutic strategies to target gut microbiomes in traumatic CNS injuries.
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Affiliation(s)
- Lahanya Guha
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat 382355, India
| | - Tejas Girish Agnihotri
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat 382355, India
| | - Aakanchha Jain
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat 382355, India
| | - Hemant Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat 382355, India.
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Zhang Z, Cheng N, Liang J, Deng Y, Xiang P, Hei Z, Li X. Gut microbiota changes in animal models of spinal cord injury: a preclinical systematic review and meta-analysis. Ann Med 2023; 55:2269379. [PMID: 37851840 PMCID: PMC10586076 DOI: 10.1080/07853890.2023.2269379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 10/06/2023] [Indexed: 10/20/2023] Open
Abstract
BACKGROUND An increasing number of studies show that the intestinal flora is closely related to spinal cord injury. Many researchers are exploring the changes in the richness, diversity, and evenness of intestinal flora in spinal cord injury animal models to identify the characteristic bacteria. METHODS A comprehensive literature search was conducted using three databases: PubMed, Embase, and Web of Science. A meta-analysis was performed using R 4.3.1 to evaluate the comparison of microbiota diversity, richness, and evenness and the relative abundance of intestinal microbiota in animals with spinal cord injury and blank controls. RESULTS Fifteen studies were included in the meta-analysis, of which 12 involved gut microbiota distribution indicators and 11 included intestinal microflora relative abundance indicators. Meta-analysis of high-dimensional indicators describing the distribution of the gut microbiota identified a substantial decline in the evenness and richness of the intestinal flora. In addition, the Actinobacteria phylum and Erysipelotrichales and Clostridiales orders were significantly different between the spinal cord injury and sham groups; therefore, they may be the characteristic bacteria in spinal cord injury models. CONCLUSION Our meta-analysis suggested that the gut microbiota in the spinal cord injury animal model group was altered compared with that in the control group, with varying degrees of changes in richness and evenness and potentially pathogenic characteristic flora. More rigorous methodological studies are needed because of the high heterogeneity and limited sample size. Further research is needed to clinically apply intestinal microbiota and potentially guide fecal microbiota transplantation therapy.
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Affiliation(s)
- Zhenye Zhang
- Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Nan Cheng
- Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jianfen Liang
- Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yifan Deng
- Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ping Xiang
- Department of Medical Quality Management, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ziqing Hei
- Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xiang Li
- Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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15
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Hamad I, Van Broeckhoven J, Cardilli A, Hellings N, Strowig T, Lemmens S, Hendrix S, Kleinewietfeld M. Effects of Recombinant IL-13 Treatment on Gut Microbiota Composition and Functional Recovery after Hemisection Spinal Cord Injury in Mice. Nutrients 2023; 15:4184. [PMID: 37836468 PMCID: PMC10574124 DOI: 10.3390/nu15194184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/06/2023] [Accepted: 09/11/2023] [Indexed: 10/15/2023] Open
Abstract
In recent years, the gut-central nervous system axis has emerged as a key factor in the pathophysiology of spinal cord injury (SCI). Interleukin-13 (IL-13) has been shown to have anti-inflammatory and neuroprotective effects in SCI. The aim of this study was to investigate the changes in microbiota composition after hemisection injury and to determine whether systemic recombinant (r)IL-13 treatment could alter the gut microbiome, indirectly promoting functional recovery. The gut microbiota composition was determined by 16S rRNA gene sequencing, and correlations between gut microbiota alterations and functional recovery were assessed. Our results showed that there were no changes in alpha diversity between the groups before and after SCI, while PERMANOVA analysis for beta diversity showed significant differences in fecal microbial communities. Phylogenetic classification of bacterial families revealed a lower abundance of the Bacteroidales S24-7 group and a higher abundance of Lachnospiraceae and Lactobacillaceae in the post-SCI group. Systemic rIL-13 treatment improved functional recovery 28 days post-injury and microbiota analysis revealed increased relative abundance of Clostridiales vadin BB60 and Acetitomaculum and decreased Anaeroplasma, Ruminiclostridium_6, and Ruminococcus compared to controls. Functional assessment with PICRUSt showed that genes related to glyoxylate cycle and palmitoleate biosynthesis-I were the predominant signatures in the rIL-13-treated group, whereas sulfolactate degradation super pathway and formaldehyde assimilation-I were enriched in controls. In conclusion, our results indicate that rIL-13 treatment promotes changes in gut microbial communities and may thereby contribute indirectly to the improvement of functional recovery in mice, possibly having important implications for the development of novel treatment options for SCI.
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Affiliation(s)
- Ibrahim Hamad
- VIB Laboratory of Translational Immunomodulation, Center for Inflammation Research (IRC), Hasselt University, 3590 Diepenbeek, Belgium (A.C.)
- Department of Immunology and Infection, Biomedical Research Institute (BIOMED), Hasselt University, 3590 Diepenbeek, Belgium; (J.V.B.); (N.H.)
| | - Jana Van Broeckhoven
- Department of Immunology and Infection, Biomedical Research Institute (BIOMED), Hasselt University, 3590 Diepenbeek, Belgium; (J.V.B.); (N.H.)
| | - Alessio Cardilli
- VIB Laboratory of Translational Immunomodulation, Center for Inflammation Research (IRC), Hasselt University, 3590 Diepenbeek, Belgium (A.C.)
- Department of Immunology and Infection, Biomedical Research Institute (BIOMED), Hasselt University, 3590 Diepenbeek, Belgium; (J.V.B.); (N.H.)
| | - Niels Hellings
- Department of Immunology and Infection, Biomedical Research Institute (BIOMED), Hasselt University, 3590 Diepenbeek, Belgium; (J.V.B.); (N.H.)
| | - Till Strowig
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany
| | - Stefanie Lemmens
- Department of Immunology and Infection, Biomedical Research Institute (BIOMED), Hasselt University, 3590 Diepenbeek, Belgium; (J.V.B.); (N.H.)
| | - Sven Hendrix
- Institute for Translational Medicine, Medical School Hamburg, 20457 Hamburg, Germany
| | - Markus Kleinewietfeld
- VIB Laboratory of Translational Immunomodulation, Center for Inflammation Research (IRC), Hasselt University, 3590 Diepenbeek, Belgium (A.C.)
- Department of Immunology and Infection, Biomedical Research Institute (BIOMED), Hasselt University, 3590 Diepenbeek, Belgium; (J.V.B.); (N.H.)
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16
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Miao Y, Fan X, Wei L, Wang B, Diao F, Fu J, Zhuang P, Zhang Y. Lizhong decoction ameliorates pulmonary infection secondary to severe traumatic brain injury in rats by regulating the intestinal physical barrier and immune response. JOURNAL OF ETHNOPHARMACOLOGY 2023; 311:116346. [PMID: 36898448 DOI: 10.1016/j.jep.2023.116346] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/26/2023] [Accepted: 02/28/2023] [Indexed: 06/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The pathogenesis of pulmonary infection secondary to severe traumatic brain injury (sTBI) is closely related to damage to the intestinal barrier. Lizhong decoction (LZD) is a prominent traditional Chinese medicine (TCM) that is widely used in clinical treatment to regulate gastrointestinal movement and enhance resistance. Nevertheless, the role and mechanism of LZD in lung infection secondary to sTBI have yet to be elucidated. AIM OF THE STUDY Here, we evaluate the therapeutic effect of LZD on pulmonary infection secondary to sTBI in rats and discuss potential regulatory mechanisms. MATERIALS AND METHODS The chemical constituents of LZD were analyzed by ultra-high performance liquid chromatography-Q Exactive-tandem mass spectrometry(UPLC-QE-MS/MS). The efficacy of LZD on rats with lung infection secondary to sTBI was examined by changes in brain morphology, coma time, brain water content, mNSS score, colony counts, 16S rRNA/RNaseP/MRP30 kDa(16S/RPP30), myeloperoxidase (MPO) content and pathology of lung tissue. The concentration of fluorescein isothiocyanate(FITC)-dextran in serum and the contents of secretory immunoglobulin A (SIgA) in colon tissue were detected by enzyme-linked immunosorbent assay (ELISA). Subsequently, Alcian Blue Periodic acid Schiff (AB-PAS) was used to detect colonic goblet cells. Immunofluorescence (IF) was used to detect the expression of tight junction proteins. The proportions of CD3+ cell, CD4+CD8+ T cells, CD45+ cell and CD103+ cells in the colon were analyzed by flow cytometry (FC). In addition, colon transcriptomics were analyzed by Illumina mRNA-Seq sequencing. Real-time quantitative polymerase chain reaction (qRT‒PCR) was used to verify the genes associated with LZD alleviation of intestinal barrier function. RESULTS Twenty-nine chemical constituents of LZD were revealed with UPLC-QE-MS/MS analysis. Administration of LZD significantly reduced colony counts, 16S/RPP30 and MPO content in lung infection secondary to sTBI rats. In addition, LZD also reduced the serum FITC-glucan content and the SIgA content of the colon. Additionally, LZD significantly increased the number of colonic goblet cells and the expression of tight junction proteins. Furthermore, LZD significantly decreased the proportion of CD3+ cell, CD4+CD8+ T cells,CD45+ and CD103+ cells in colon tissue. Transcriptomic analysis identified 22 upregulated genes and 56 downregulated genes in sTBI compared to the sham group. The levels of seven genes were recovered after LZD treatment. qRT‒PCR successfully validated two genes (Jchain and IL-6) at the mRNA level. CONCLUSION LZD can improves sTBI secondary lung infection by regulating the intestinal physical barrier and immune response. Thees results suggested that LZD may be a prospective treatment for pulmonary infection secondary to sTBI.
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Affiliation(s)
- Yulu Miao
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xuejin Fan
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Luge Wei
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Bin Wang
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Fengyin Diao
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jiafeng Fu
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Pengwei Zhuang
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
| | - Yanjun Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Department of Integrated Rehabilitation, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
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17
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Ortega MA, Fraile-Martinez O, García-Montero C, Haro S, Álvarez-Mon MÁ, De Leon-Oliva D, Gomez-Lahoz AM, Monserrat J, Atienza-Pérez M, Díaz D, Lopez-Dolado E, Álvarez-Mon M. A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities. Mil Med Res 2023; 10:26. [PMID: 37291666 PMCID: PMC10251601 DOI: 10.1186/s40779-023-00461-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 06/01/2023] [Indexed: 06/10/2023] Open
Abstract
Spinal cord injury (SCI) is a devastating and disabling medical condition generally caused by a traumatic event (primary injury). This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage (secondary injury). The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI, explaining the progression and detrimental consequences related to this condition. Psychoneuroimmunoendocrinology (PNIE) is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism, considering the mind and the body as a whole. The initial traumatic event and the consequent neurological disruption trigger immune, endocrine, and multisystem dysfunction, which in turn affect the patient's psyche and well-being. In the present review, we will explore the most important local and systemic consequences of SCI from a PNIE perspective, defining the changes occurring in each system and how all these mechanisms are interconnected. Finally, potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.
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Affiliation(s)
- Miguel A. Ortega
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Sergio Haro
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Miguel Ángel Álvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain
| | - Diego De Leon-Oliva
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Ana M. Gomez-Lahoz
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Jorge Monserrat
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Mar Atienza-Pérez
- Service of Rehabilitation, National Hospital for Paraplegic Patients, Carr. de la Peraleda, S/N, 45004 Toledo, Spain
| | - David Díaz
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Elisa Lopez-Dolado
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain
| | - Melchor Álvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Immune System Diseases-Rheumatology Service and Internal Medicine, University Hospital Príncipe de Asturias (CIBEREHD), 28806 Alcala de Henares, Spain
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Knibbe CA, Ahmed RU, Wilkins F, Sharma M, Ethridge J, Morgan M, Gibson D, Cooper KB, Howland DR, Vadhanam MV, Barve SS, Davison S, Sherwood LC, Semler J, Abell T, Boakye M. SmartPill™ Administration to Assess Gastrointestinal Function after Spinal Cord Injury in a Porcine Model-A Preliminary Study. Biomedicines 2023; 11:1660. [PMID: 37371755 DOI: 10.3390/biomedicines11061660] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/02/2023] [Accepted: 06/04/2023] [Indexed: 06/29/2023] Open
Abstract
Gastrointestinal (GI) complications, including motility disorders, metabolic deficiencies, and changes in gut microbiota following spinal cord injury (SCI), are associated with poor outcomes. After SCI, the autonomic nervous system becomes unbalanced below the level of injury and can lead to severe GI dysfunction. The SmartPill™ is a non-invasive capsule that, when ingested, transmits pH, temperature, and pressure readings that can be used to assess effects in GI function post-injury. Our minipig model allows us to assess these post-injury changes to optimize interventions and ultimately improve GI function. The aim of this study was to compare pre-injury to post-injury transit times, pH, and pressures in sections of GI tract by utilizing the SmartPill™ in three pigs after SCI at 2 and 6 weeks. Tributyrin was administered to two pigs to assess the influences on their gut microenvironment. We observed prolonged GET (Gastric Emptying Time) and CTT (Colon Transit Time), decreases in contraction frequencies (Con freq) in the antrum of the stomach, colon, and decreases in duodenal pressures post-injury. We noted increases in Sum amp generated at 2 weeks post-injury in the colon, with corresponding decreases in Con freq. We found transient changes in pH in the colon and small intestine at 2 weeks post-injury, with minimal effect on stomach pH post-injury. Prolonged GETs and CTTs can influence the absorptive profile in the gut and contribute to pathology development. This is the first pilot study to administer the SmartPill™ in minipigs in the context of SCI. Further investigations will elucidate these trends and characterize post-SCI GI function.
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Affiliation(s)
- Chase A Knibbe
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
| | - Rakib Uddin Ahmed
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
| | - Felicia Wilkins
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
| | - Mayur Sharma
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
| | - Jay Ethridge
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
| | - Monique Morgan
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
| | - Destiny Gibson
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
| | - Kimberly B Cooper
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
| | - Dena R Howland
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
- Research Service, Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA
| | - Manicka V Vadhanam
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Louisville, Louisville, KY 40202, USA
| | - Shirish S Barve
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Louisville, Louisville, KY 40202, USA
| | - Steven Davison
- Comparative Medicine Research Unit, University of Louisville, Louisville, KY 40202, USA
| | - Leslie C Sherwood
- Comparative Medicine Research Unit, University of Louisville, Louisville, KY 40202, USA
| | | | - Thomas Abell
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Louisville, Louisville, KY 40202, USA
| | - Maxwell Boakye
- Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40202, USA
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Liu P, Liu M, Xi D, Bai Y, Ma R, Mo Y, Zeng G, Zong S. Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17 + γδ T cells. J Zhejiang Univ Sci B 2023; 24:312-325. [PMID: 37056207 PMCID: PMC10106403 DOI: 10.1631/jzus.b2200417] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 12/30/2022] [Indexed: 04/15/2023]
Abstract
Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.
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Affiliation(s)
- Pan Liu
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
- Department of Orthopaedics, the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, China
| | - Mingfu Liu
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Deshuang Xi
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Yiguang Bai
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
- Department of Orthopaedics, Nanchong Central Hosipital, the Second Clinical Institute of North Sichuan Medical College, Nanchong 637000, China
| | - Ruixin Ma
- Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning 530021, China
| | - Yaomin Mo
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Gaofeng Zeng
- College of Public Hygiene of Guangxi Medical University, Nanning 530021, China.
| | - Shaohui Zong
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
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20
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Wulf MJ, Tom VJ. Consequences of spinal cord injury on the sympathetic nervous system. Front Cell Neurosci 2023; 17:999253. [PMID: 36925966 PMCID: PMC10011113 DOI: 10.3389/fncel.2023.999253] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 02/09/2023] [Indexed: 03/06/2023] Open
Abstract
Spinal cord injury (SCI) damages multiple structures at the lesion site, including ascending, descending, and propriospinal axons; interrupting the conduction of information up and down the spinal cord. Additionally, axons associated with the autonomic nervous system that control involuntary physiological functions course through the spinal cord. Moreover, sympathetic, and parasympathetic preganglionic neurons reside in the spinal cord. Thus, depending on the level of an SCI, autonomic function can be greatly impacted by the trauma resulting in dysfunction of various organs. For example, SCI can lead to dysregulation of a variety of organs, such as the pineal gland, the heart and vasculature, lungs, spleen, kidneys, and bladder. Indeed, it is becoming more apparent that many disorders that negatively affect quality-of-life for SCI individuals have a basis in dysregulation of the sympathetic nervous system. Here, we will review how SCI impacts the sympathetic nervous system and how that negatively impacts target organs that receive sympathetic innervation. A deeper understanding of this may offer potential therapeutic insight into how to improve health and quality-of-life for those living with SCI.
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Affiliation(s)
| | - Veronica J. Tom
- Marion Murray Spinal Cord Research Center, Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, United States
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21
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Rouchka EC, de Almeida C, House RB, Daneshmand JC, Chariker JH, Saraswat-Ohri S, Gomes C, Sharp M, Shum-Siu A, Cesarz GM, Petruska JC, Magnuson DS. Construction of a searchable database for gene expression changes in spinal cord injury experiments. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.02.01.526630. [PMID: 36778366 PMCID: PMC9915599 DOI: 10.1101/2023.02.01.526630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Spinal cord injury (SCI) is a debilitating disease resulting in an estimated 18,000 new cases in the United States on an annual basis. Significant behavioral research on animal models has led to a large amount of data, some of which has been catalogued in the Open Data Commons for Spinal Cord Injury (ODC-SCI). More recently, high throughput sequencing experiments have been utilized to understand molecular mechanisms associated with SCI, with nearly 6,000 samples from over 90 studies available in the Sequence Read Archive. However, to date, no resource is available for efficiently mining high throughput sequencing data from SCI experiments. Therefore, we have developed a protocol for processing RNA-Seq samples from high-throughput sequencing experiments related to SCI resulting in both raw and normalized data that can be efficiently mined for comparisons across studies as well as homologous discovery across species. We have processed 1,196 publicly available RNA-seq samples from 50 bulk RNA-Seq studies across nine different species, resulting in an SQLite database that can be used by the SCI research community for further discovery. We provide both the database as well as a web-based front-end that can be used to query the database for genes of interest, differential gene expression, genes with high variance, and gene set enrichments.
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Affiliation(s)
- Eric C. Rouchka
- Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, University of Louisville, Louisville, KY USA
- Kentucky IDeA Networks of Biomedical Research Excellence (KY INBRE) Bioinformatics Core, University of Louisville School of Medicine, 522 East Gray Street, Louisville, KY USA 40202
- Bioinformatics Program, School of Interdisciplinary and Graduate Studies, University of Louisville, Louisville, KY
| | - Carlos de Almeida
- Translational Neuroscience Program, School of Interdisciplinary and Graduate Studies, University of Louisville, Louisville, KY
- Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY
| | - Randi B. House
- Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY
- Department of Bioengineering, Speed School of Engineering, University of Louisville, Louisville, KY
| | - Jonah C. Daneshmand
- Bioinformatics Program, School of Interdisciplinary and Graduate Studies, University of Louisville, Louisville, KY
| | - Julia H. Chariker
- Kentucky IDeA Networks of Biomedical Research Excellence (KY INBRE) Bioinformatics Core, University of Louisville School of Medicine, 522 East Gray Street, Louisville, KY USA 40202
- Department of Neuroscience Training, School of Medicine, University of Louisville, Louisville, KY
| | - Sujata Saraswat-Ohri
- Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY
- Department of Neurological Surgery, School of Medicine, University of Louisville, Louisville, KY USA
| | - Cynthia Gomes
- Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY
- Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, KY
| | - Morgan Sharp
- Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY
- Department of Neurological Surgery, School of Medicine, University of Louisville, Louisville, KY USA
| | - Alice Shum-Siu
- Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY
- Department of Neurological Surgery, School of Medicine, University of Louisville, Louisville, KY USA
| | - Greta M. Cesarz
- Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY
| | - Jeffrey C. Petruska
- Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY
- Department of Neurological Surgery, School of Medicine, University of Louisville, Louisville, KY USA
- Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, KY
| | - David S.K. Magnuson
- Translational Neuroscience Program, School of Interdisciplinary and Graduate Studies, University of Louisville, Louisville, KY
- Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY
- Department of Neurological Surgery, School of Medicine, University of Louisville, Louisville, KY USA
- Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, KY
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22
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Gut microbiota in chronic pain: Novel insights into mechanisms and promising therapeutic strategies. Int Immunopharmacol 2023. [DOI: 10.1016/j.intimp.2023.109685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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23
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McCoubrey LE, Favaron A, Awad A, Orlu M, Gaisford S, Basit AW. Colonic drug delivery: Formulating the next generation of colon-targeted therapeutics. J Control Release 2023; 353:1107-1126. [PMID: 36528195 DOI: 10.1016/j.jconrel.2022.12.029] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/08/2022] [Accepted: 12/10/2022] [Indexed: 12/26/2022]
Abstract
Colonic drug delivery can facilitate access to unique therapeutic targets and has the potential to enhance drug bioavailability whilst reducing off-target effects. Delivering drugs to the colon requires considered formulation development, as both oral and rectal dosage forms can encounter challenges if the colon's distinct physiological environment is not appreciated. As the therapeutic opportunities surrounding colonic drug delivery multiply, the success of novel pharmaceuticals lies in their design. This review provides a modern insight into the key parameters determining the effective design and development of colon-targeted medicines. Influential physiological features governing the release, dissolution, stability, and absorption of drugs in the colon are first discussed, followed by an overview of the most reliable colon-targeted formulation strategies. Finally, the most appropriate in vitro, in vivo, and in silico preclinical investigations are presented, with the goal of inspiring strategic development of new colon-targeted therapeutics.
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Affiliation(s)
- Laura E McCoubrey
- 29 - 39 Brunswick Square, UCL School of Pharmacy, University College London, London, WC1N 1AX, UK
| | - Alessia Favaron
- 29 - 39 Brunswick Square, UCL School of Pharmacy, University College London, London, WC1N 1AX, UK
| | - Atheer Awad
- 29 - 39 Brunswick Square, UCL School of Pharmacy, University College London, London, WC1N 1AX, UK
| | - Mine Orlu
- 29 - 39 Brunswick Square, UCL School of Pharmacy, University College London, London, WC1N 1AX, UK
| | - Simon Gaisford
- 29 - 39 Brunswick Square, UCL School of Pharmacy, University College London, London, WC1N 1AX, UK
| | - Abdul W Basit
- 29 - 39 Brunswick Square, UCL School of Pharmacy, University College London, London, WC1N 1AX, UK.
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24
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Lalonde R, Strazielle C. Probiotic Influences on Motor Skills: A Review. Curr Neuropharmacol 2023; 21:2481-2486. [PMID: 37550907 PMCID: PMC10616912 DOI: 10.2174/1570159x21666230807150523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/20/2023] [Accepted: 03/05/2023] [Indexed: 08/09/2023] Open
Abstract
The effects of probiotics have mostly been shown to be favorable on measures of anxiety and stress. More recent experiments indicate single- and multi-strain probiotics in treating motorrelated diseases. Initial studies in patients with Parkinson's disease and Prader-Willi syndrome are concordant with this hypothesis. In addition, probiotics improved motor coordination in normal animals and models of Parkinson's disease, multiple sclerosis, and spinal cord injury as well as grip strength in hepatic encephalopathy. Further studies should delineate the most optimal bacterial profile under each condition.
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Affiliation(s)
- Robert Lalonde
- Laboratory of Stress, Immunity, Pathogens (EA7300), Medical School, University of Lorraine, 54500, Vandœuvre-les-Nancy, France
| | - Catherine Strazielle
- Laboratory of Stress, Immunity, Pathogens (EA7300), Medical School, University of Lorraine, 54500, Vandœuvre-les-Nancy, France
- CHRU Nancy, Vandœuvre-les-Nancy, France
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25
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Willman J, Willman M, Reddy R, Fusco A, Sriram S, Mehkri Y, Charles J, Goeckeritz J, Lucke‐Wold B. Gut microbiome and neurosurgery: Implications for treatment. CLINICAL AND TRANSLATIONAL DISCOVERY 2022; 2. [PMID: 36268259 PMCID: PMC9577538 DOI: 10.1002/ctd2.139] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 09/19/2022] [Indexed: 11/06/2022]
Abstract
AbstractIntroductionThe aim of this review is to summarize the current understanding of the gut‐brain axis (GBA), its impact on neurosurgery, and its implications for future treatment.BackgroundAn abundance of research has established the existence of a collection of pathways between the gut microbiome and the central nervous system (CNS), commonly known as the GBA. Complicating this relationship, the gut microbiome bacterial diversity appears to change with age, antibiotic exposure and a number of external and internal factors.MethodsIn this paper, we present the current understanding of the key protective and deleterious roles the gut microbiome plays in the pathogenesis of several common neurosurgical concerns.ResultsSpecifically, we examine how spinal cord injury, traumatic brain injury and stroke may cause gut microbial dysbiosis. Furthermore, this link appears to be bidirectional as gut dysbiosis contributes to secondary CNS injury in each of these ailment settings. This toxic cycle may be broken, and the future secondary damage rescued by timely, therapeutic, gut microbiome modification. In addition, a robust gut microbiome appears to improve outcomes in brain tumour treatment. There are several primary routes by which microbiome dysbiosis may be ameliorated, including faecal microbiota transplant, oral probiotics, bacteriophages, genetic modification of gut microbiota and vagus nerve stimulation.ConclusionThe GBA represents an important component of patient care in the field of neurosurgery. Future research may illuminate ideal methods of therapeutic microbiome modulation in distinct pathogenic settings.
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Affiliation(s)
- Jonathan Willman
- College of Medicine University of Florida Gainesville Florida USA
| | - Matthew Willman
- College of Medicine University of Florida Gainesville Florida USA
| | - Ramya Reddy
- College of Medicine University of Florida Gainesville Florida USA
| | - Anna Fusco
- College of Medicine University of Florida Gainesville Florida USA
| | - Sai Sriram
- College of Medicine University of Florida Gainesville Florida USA
| | - Yusuf Mehkri
- College of Medicine University of Florida Gainesville Florida USA
| | - Jude Charles
- Department of Neurosurgery Jackson Memorial Hospital Miami Florida USA
| | - Joel Goeckeritz
- College of Medicine University of Florida Gainesville Florida USA
| | - Brandon Lucke‐Wold
- Department of Neurosurgery University of Florida Gainesville Florida USA
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26
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Kang JN, Sun ZF, Li XY, Zhang XD, Jin ZX, Zhang C, Zhang Y, Wang HY, Huang NN, Jiang JH, Ning B. Alterations in gut microbiota are related to metabolite profiles in spinal cord injury. Neural Regen Res 2022; 18:1076-1083. [PMID: 36254996 PMCID: PMC9827763 DOI: 10.4103/1673-5374.355769] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8-T10 traumatic spinal cord injury. We used 16S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids (L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.
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Affiliation(s)
- Jian-Ning Kang
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Zheng-Fang Sun
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Xin-Yu Li
- Department of Spinal Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
| | - Xiao-Di Zhang
- School of Clinical Medicine, Weifang Medical University, Weifang, Shandong Province, China
| | - Zheng-Xin Jin
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Ce Zhang
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Ying Zhang
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Hui-Yun Wang
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Na-Na Huang
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Jian-Hao Jiang
- Department of Spinal Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China,Department of Traumatic Orthopedics, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong Province, China,Correspondence to: Bin Ning, ; Jian-Hao Jiang, .
| | - Bin Ning
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China,Department of Spinal Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China,Correspondence to: Bin Ning, ; Jian-Hao Jiang, .
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27
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Smith AM, Welch BA, Harris KK, Garrett MR, Grayson BE. Nutrient composition influences the gut microbiota in chronic thoracic spinal cord-injured rats. Physiol Genomics 2022; 54:402-415. [PMID: 36036458 PMCID: PMC9576181 DOI: 10.1152/physiolgenomics.00037.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 08/03/2022] [Accepted: 08/22/2022] [Indexed: 11/22/2022] Open
Abstract
Chronic spinal cord injury (SCI) results in an increased predisposition to various metabolic problems that can be exacerbated by consuming a diet rich in calories and saturated fat. In addition, gastrointestinal symptoms have been reported after SCI, including intestinal dysbiosis of the gut microbiome. The effects of both diet and SCI on the gut microbiome of adult male Long Evans rats euthanized 16 wk after injury were investigated. The rats were either thoracic spinal contused or received sham procedures. After 12 wk of either a low-fat or high-fat diet, cecal contents were analyzed, revealing significant microbial changes to every taxonomic level below the kingdom level. Shannon α diversity analyses demonstrated a significant difference in diversity between the groups based on the surgical condition of the rats. SCI produced a unique signature of changes in commensal bacteria that were significantly different than Sham. Specific changes in commensal bacteria as a result of diet manipulation had high fidelity with reports in the literature, such as Clostridia, Thiohalorhabdales, and Pseudomonadales. In addition, novel changes in commensal bacteria were identified that are unique dietary influences on SCI. Linear regression analysis on body fat and lean mass showed that a consequence of chronic SCI produces uncoupled associations between some commensal bacteria and body composition. In conclusion, despite tightly controlling the protein content and varying the carbohydrate and fat contents, Sham and SCI rats respond uniquely to diet. These data provide potential direction for therapeutic modulation of the microbiome to improve health and wellness following SCI.
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Affiliation(s)
- Allie M Smith
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi
| | - Bradley A Welch
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi
| | - Kwamie K Harris
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi
| | - Michael R Garrett
- Department of Pharmacology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Bernadette E Grayson
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi
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28
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Krakovski MA, Arora N, Jain S, Glover J, Dombrowski K, Hernandez B, Yadav H, Sarma AK. Diet-microbiome-gut-brain nexus in acute and chronic brain injury. Front Neurosci 2022; 16:1002266. [PMID: 36188471 PMCID: PMC9523267 DOI: 10.3389/fnins.2022.1002266] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
In recent years, appreciation for the gut microbiome and its relationship to human health has emerged as a facilitator of maintaining healthy physiology and a contributor to numerous human diseases. The contribution of the microbiome in modulating the gut-brain axis has gained significant attention in recent years, extensively studied in chronic brain injuries such as Epilepsy and Alzheimer’s Disease. Furthermore, there is growing evidence that gut microbiome also contributes to acute brain injuries like stroke(s) and traumatic brain injury. Microbiome-gut-brain communications are bidirectional and involve metabolite production and modulation of immune and neuronal functions. The microbiome plays two distinct roles: it beneficially modulates immune system and neuronal functions; however, abnormalities in the host’s microbiome also exacerbates neuronal damage or delays the recovery from acute injuries. After brain injury, several inflammatory changes, such as the necrosis and apoptosis of neuronal tissue, propagates downward inflammatory signals to disrupt the microbiome homeostasis; however, microbiome dysbiosis impacts the upward signaling to the brain and interferes with recovery in neuronal functions and brain health. Diet is a superlative modulator of microbiome and is known to impact the gut-brain axis, including its influence on acute and neuronal injuries. In this review, we discussed the differential microbiome changes in both acute and chronic brain injuries, as well as the therapeutic importance of modulation by diets and probiotics. We emphasize the mechanistic studies based on animal models and their translational or clinical relationship by reviewing human studies.
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Affiliation(s)
| | - Niraj Arora
- Department of Neurology, University of Missouri, Columbia, MO, United States
| | - Shalini Jain
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, United States
| | - Jennifer Glover
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, United States
| | - Keith Dombrowski
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, United States
| | - Beverly Hernandez
- Clinical Nutrition Services, Tampa General Hospital, Tampa, FL, United States
| | - Hariom Yadav
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, United States
- USF Center for Microbiome Research, Microbiomes Institute, University of South Florida, Tampa, FL, United States
- *Correspondence: Hariom Yadav,
| | - Anand Karthik Sarma
- Wake Forest University School of Medicine, Winston-Salem, NC, United States
- Department of Neurology, Atrium Health Wake Forest Baptist, Winston-Salem, NC, United States
- Anand Karthik Sarma,
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Zhang Z, Sui R, Ge L, Xia D. Moxibustion exhibits therapeutic effects on spinal cord injury via modulating microbiota dysbiosis and macrophage polarization. Aging (Albany NY) 2022; 14:5800-5811. [PMID: 35876627 PMCID: PMC9365548 DOI: 10.18632/aging.204184] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 06/14/2022] [Indexed: 11/25/2022]
Abstract
In this study, we aimed to study the effect of moxibustion (MOX) on microbiota dysbiosis and macrophage polarization, so as to unveil the mechanism underlying the therapeutic effect of MOX in the management of spinal cord injury (SCI). SCI animal models were established to study the effect of MOX. Accordingly, it was found that MOX treatment significantly suppressed the Ace index and Shannon index in the SCI group. Moreover, the reduced relative levels of Lactobacillales and Bifidobacteriales and the elevated relative level of Clostridiales in the SCI animals were mitigated by the treatment of MOX. The body weight, food intake, energy expenditure (EE) index and respiratory quotient (RQ) index of SCI mice were all evidently decreased, but the levels of interleukin (IL)-17, interferon (IFN)-γ, monocyte chemoattractant protein-1 (MCP-1) and IL-1β were increased in the SCI group. Moreover, MOX treatment significantly mitigated the dysregulation of above factors in SCI mice. Accordingly, we found that the Basso Mouse Scale (BMS) score was negatively correlated with the level of Clostridiales while positively correlated with the level of Lactobacillales. The apoptotic index and caspase-3 level were both evidently increased in the SCI group, while the SCI+MOX group showed reduced levels of apoptotic index and caspase-3. Therefore, it can be concluded that the treatment with MOX can promote microbiota dysbiosis and macrophage polarization, thus alleviating spinal cord injury by down-regulating the expression of inflammatory cytokines.
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Affiliation(s)
- Zhuang Zhang
- Department of Neurology, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, Liaoning 121012, China
| | - Rubo Sui
- Department of Neurology, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, Liaoning 121012, China
| | - Lili Ge
- Department of Ultrasound, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, Liaoning 121012, China
| | - Dongjian Xia
- Department of Neurosurgery, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, Liaoning 121012, China
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Hamilton AM, Sampson TR. Traumatic spinal cord injury and the contributions of the post-injury microbiome. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 167:251-290. [PMID: 36427958 DOI: 10.1016/bs.irn.2022.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Spinal cord injuries are an enormous burden on injured individuals and their caregivers. The pathophysiological effects of injury are not limited to the spine and limb function, but affect numerous body systems. Growing observations in human studies and experimental models suggest that the gut microbiome is altered following spinal cord injury. Given the importance of signals derived from the gut microbiome for host physiology, it is possible that injury-triggered dysbiosis subsequently affects aspects of recovery. Here, we review emerging literature on the role of the microbiome following spinal cord injury. Specifically, we highlight findings from both human and experimental studies that correlate taxonomic changes to aspects of injury recovery. Examination of both observational and emerging interventional studies supports the notion that future therapeutic avenues for spinal cord injury pathologies may lie at the interface of the host and indigenous microbes.
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Affiliation(s)
- Adam M Hamilton
- Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, United States
| | - Timothy R Sampson
- Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, United States.
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31
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Pathophysiology, Classification and Comorbidities after Traumatic Spinal Cord Injury. J Pers Med 2022; 12:jpm12071126. [PMID: 35887623 PMCID: PMC9323191 DOI: 10.3390/jpm12071126] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/26/2022] [Accepted: 06/27/2022] [Indexed: 12/25/2022] Open
Abstract
The spinal cord is a conduit within the central nervous system (CNS) that provides ongoing communication between the brain and the rest of the body, conveying complex sensory and motor information necessary for safety, movement, reflexes, and optimization of autonomic function. After a spinal cord injury (SCI), supraspinal influences on the spinal segmental control system and autonomic nervous system (ANS) are disrupted, leading to spastic paralysis, pain and dysesthesia, sympathetic blunting and parasympathetic dominance resulting in cardiac dysrhythmias, systemic hypotension, bronchoconstriction, copious respiratory secretions and uncontrolled bowel, bladder, and sexual dysfunction. This article outlines the pathophysiology of traumatic SCI, current and emerging methods of classification, and its influence on sensory/motor function, and introduces the probable comorbidities associated with SCI that will be discussed in more detail in the accompanying manuscripts of this special issue.
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Miao Y, Wang B, Hu J, Zhang H, Li X, Huang Y, Zhuang P, Zhang Y. Herb Formula (GCis) Prevents Pulmonary Infection Secondary to Intracerebral Hemorrhage by Enhancing Peripheral Immunity and Intestinal Mucosal Immune Barrier. Front Pharmacol 2022; 13:888684. [PMID: 35677425 PMCID: PMC9168277 DOI: 10.3389/fphar.2022.888684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 04/04/2022] [Indexed: 11/13/2022] Open
Abstract
Lung infection is a common complication induced by stroke and seriously affects the prognosis and life quality of patients. However, effective therapeutic strategies are still lacking. In the present study, the herb formula GCis was confirmed to prevent pulmonary infection induced by intracerebral hemorrhage (ICH). The animal model of lung infection induced by ICH, GCis (Ginseng Radix et Rhizoma, Aconiti Lateralis Radix Praeparata, and Cistanches Herba) was orally administrated every day for 7 days. Lung microbial biomass and pathological results showed that the GCis formula pretreatment significantly reduced lung bacterial biomass and alleviated pathological abnormalities. These results indicated that the GCis formula has a clear pharmacological effect on preventing lung infection induced by ICH. Immunosuppression induced by ICH seemed to be the main mechanism of lung infection. Our results showed that the spleen and thymus indexes, WBC, and LY% contents were significantly increased in the GCis formula group. Moreover, bone marrow cells were further analyzed by transcriptome sequencing, and GO and KEGG enrichment analysis results showed that immune function was the main pathway enriched by differential genes after GCis formula intervention. More importantly, our results showed that GCis pretreatment had no significant effect on the mRNA expression of IL-1β, IL-6, and TNF-α in the brain. These results indicated that the GCis formula could enhance immunity after ICH. The intestinal barrier function was further investigated in the present study, considering the origin of the source of infection. Our results showed that the mRNA expressions of intestinal ZO-1, SIgA, and MUC2 were significantly increased, villi structure was intact, inflammatory cell infiltration was reduced, and goblet cell number was increased after GCis formula treatment. These results suggest that the GCis formula can enhance the intestinal mucosal immune barrier. This study provides a herb formula (GCis) that could enhance peripheral immunity and intestinal mucosal immune barrier to prevent pulmonary infection induced by ICH. It would be beneficial in the prevention of severe clinical infections.
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Affiliation(s)
- Yulu Miao
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Bin Wang
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jing Hu
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Hanyu Zhang
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaojin Li
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yingying Huang
- College of Pharmacy, Anhui University of Chinese Medicine and Anhui Academy of Chinese Medicine, Hefei, China
| | - Pengwei Zhuang
- Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yanjun Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Rong ZJ, Cai HH, Wang H, Liu GH, Zhang ZW, Chen M, Huang YL. Ursolic Acid Ameliorates Spinal Cord Injury in Mice by Regulating Gut Microbiota and Metabolic Changes. Front Cell Neurosci 2022; 16:872935. [PMID: 35602557 PMCID: PMC9115468 DOI: 10.3389/fncel.2022.872935] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 03/28/2022] [Indexed: 02/02/2023] Open
Abstract
Background: Spinal cord injury (SCI) damages the autonomic nervous system and affects the homeostasis of gut microbiota. Ursolic acid (UA) is a candidate drug for treating nervous system injury due to its neuroprotective and antioxidant functions. The purpose of our study was to investigate the role of UA on SCI and its mechanism. Methods: UA was administered to SCI mice and the solvent corn oil was used as control. The weight of the mice was recorded daily. Mice feces were collected 21 days after surgery for 16S rRNA-amplicon sequencing and untargeted metabolomics analysis. The expressions of NF-κB, IL-1β, and TNF-α in the spinal cord and colon tissues of mice were detected by Western blot and Enzyme-linked immunosorbent assay, respectively. Immunohistochemistry was used to analyze the expression of NeuN, NF-200, and synapsin in the spinal cord tissues. Results: UA treatment increased body weight and soleus muscle weight of SCI mice. UA treatment inhibited inflammatory response and protected neuronal activity in SCI mice. UA improved the relative abundance of Muribaculaceae, Lachnospiraceae_NK4A136_group, and Alloprevotell genus in the gut tract of SCI mice. SCI destroyed the Glutamine_and_D-glutamate_metabolism, Nitrogen_metabolism, Aminoacyl-tRNA_biosynthesis, and Taurine_and_hypotaurine_metabolism in the gut of mice, which might be alleviated by UA. Conclusions: UA treatment could inhibit SCI progression by improving the gut environment and metabolic changes, promoting synaptic regeneration and anti-inflammatory effects.
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Affiliation(s)
- Zi-Jie Rong
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China
- Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
| | - Hong-Hua Cai
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China
- Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
| | - Hao Wang
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China
- Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
| | - Gui-Hua Liu
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China
- Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
| | - Zhi-Wen Zhang
- Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
- Department of Orthopaedics, Huizhou Municipal Central Hospital, Huizhou, China
| | - Min Chen
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China
- Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
- *Correspondence: Min Chen Yu-Liang Huang
| | - Yu-Liang Huang
- Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
- Department of Orthopaedics, Huizhou Municipal Central Hospital, Huizhou, China
- *Correspondence: Min Chen Yu-Liang Huang
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Optical Coherence Tomography Angiography and Attenuation Imaging for Label-Free Observation of Functional Changes in the Intestine after Sympathectomy: A Pilot Study. PHOTONICS 2022. [DOI: 10.3390/photonics9050304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
We present in this study optical coherence tomography angiography (OCTA) and OCT attenuation imaging (OCTAI) for in vivo non-destructive visualization of intramural blood and lymphatic vessels of the intestine wall. Rabbit small intestine in the norm and after thoracolumbar sympathectomy served as the object of the intraoperative study. Compared to OCTA real-time imaging, OCTAI takes several minutes and can be termed as “nearly real time”. OCTAI signal processing was modified to take into account the signal-to-noise ratio and the final thickness of the intestine wall. The results showed that, after sympathectomy, changes in functioning of intramural blood and lymphatic vessels were observed with a high statistical significance. The occurrence of trauma-induced constriction of the blood and lymphatic vessels led to an especially pronounced decrease in the length of small-caliber (<30 µm) blood vessels (p < 10−5), as well as in the volumetric density of lymphatic vessels (on average by ~50%) compared to their initial state. Remarkably, OCTA/OCTAI modalities provide the unique ability for “nearly-instant detection” of changes in functional status of the tissues, long before they become visible on histology. The proposed approach can be used in further experiments to clarify the mechanisms of changes in intestinal blood and lymph flows in response to trauma of the nervous system. Furthermore, potentially it can be used intraoperatively in patients requiring express diagnosis of the state of intramural blood and lymph circulation.
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Glisic M, Flueck JL, Ruettimann B, Hertig-Godeschalk A, Valido E, Bertolo A, Stucki G, Stoyanov J. The feasibility of a crossover, randomized controlled trial design to assess the effect of probiotics and prebiotics on health of elite Swiss para-athletes: a study protocol. Pilot Feasibility Stud 2022; 8:94. [PMID: 35477496 PMCID: PMC9044645 DOI: 10.1186/s40814-022-01048-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 04/04/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Spinal cord injury (SCI) may cause an autonomic imbalance in the gastrointestinal tract, leading to deficits in colonic motility, mucosal secretions, vascular tone, and an increase of intestinal barrier permeability. Autonomic denervation and factors such as age, physical activity, antibiotic use and stress may cause intestinal bacterial translocation, decreased microbiota diversity, known as gut dysbiosis and thus increase susceptibility to experiencing gastrointestinal discomfort. Probiotic treatment in individuals with SCI may normalize the gut microbiota and improve overall health. We aim to assess the feasibility of probiotic and prebiotic intervention in athletes with SCI and collect information necessary for sample size calculation of a definite trial on improving health outcomes in para-athletes. METHODS AND ANALYSIS Elite Swiss para-athletes (aged> 18 years), being shortlisted for the Paralympic Games 2021 in Tokyo or a member of a national team (n = 43), will be invited to participate in this single-center randomized crossover trial. Athletes suffering from chronic inflammatory bowel diseases, those currently taking antibiotics or other medication to alleviate gastro-intestinal complaints will not be eligible to be included in the study. Athletes will be randomized (1:1) to receive for 4 weeks a daily dose of either 3 g of probiotic preparation or 5 g of prebiotic (organic oat bran) supplementation in addition to usual diet, followed by a 4-week washout period or vice versa. The primary outcome is the feasibility of the study, measured by recruitment and dropout rates, feasibility of the measurements, acceptability and adherence to the intervention. Secondary outcomes include gastrointestinal health assessment, diet and training information, handgrip strength, blood diagnostic parameters, and intestinal microbiome characterization. The changes in clinically relevant secondary outcome values will be used to make a power calculation for definite trial. DISCUSSION This pilot trial will address two common challenges in SCI research: the difficulty to recruit enough participants for a sufficiently powered study and the ability to collect data within the limits of a realistic budget and time frame. Upon demonstrated feasibility of the intervention and study procedures, the intervention will be evaluated in a definitive controlled trial comprising a larger sample of para-athletes (elite, engaged, or recreationally active) individuals with a SCI. TRIAL REGISTRATION NCT04659408.
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Affiliation(s)
- Marija Glisic
- Swiss Paraplegic Research, Guido A. Zäch Strasse 4, CH-6207, Nottwil, Switzerland.,Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, CH-3012, Bern, Switzerland
| | - Joelle L Flueck
- Sports Medicine, Swiss Paraplegic Centre, CH-6207, Nottwil, Switzerland
| | | | | | - Ezra Valido
- Swiss Paraplegic Research, Guido A. Zäch Strasse 4, CH-6207, Nottwil, Switzerland
| | - Alessandro Bertolo
- Swiss Paraplegic Research, Guido A. Zäch Strasse 4, CH-6207, Nottwil, Switzerland
| | - Gerold Stucki
- Swiss Paraplegic Research, Guido A. Zäch Strasse 4, CH-6207, Nottwil, Switzerland
| | - Jivko Stoyanov
- Swiss Paraplegic Research, Guido A. Zäch Strasse 4, CH-6207, Nottwil, Switzerland. .,Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, CH-3012, Bern, Switzerland.
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Musleh-Vega S, Ojeda J, Vidal PM. Gut Microbiota–Brain Axis as a Potential Modulator of Psychological Stress after Spinal Cord Injury. Biomedicines 2022; 10:biomedicines10040847. [PMID: 35453597 PMCID: PMC9024710 DOI: 10.3390/biomedicines10040847] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/01/2022] [Accepted: 04/02/2022] [Indexed: 12/12/2022] Open
Abstract
A growing body of evidence from preclinical and clinical studies has associated alterations of the gut microbiota–brain axis with the progression and development of a number of pathological conditions that also affect cognitive functions. Spinal cord injuries (SCIs) can be produced from traumatic and non-traumatic causes. It has been reported that SCIs are commonly associated with anxiety and depression-like symptoms, showing an incidence range between 11 and 30% after the injury. These psychological stress-related symptoms are associated with worse prognoses in SCIs and have been attributed to psychosocial stressors and losses of independence. Nevertheless, emotional and mental modifications after SCI could be related to changes in the volume of specific brain areas associated with information processing and emotions. Additionally, physiological modifications have been recognized as a predisposing factor for mental health depletion, including the development of gut dysbiosis. This condition of imbalance in microbiota composition has been shown to be associated with depression in clinical and pre-clinical models. Therefore, the understanding of the mechanisms underlying the relationship between SCIs, gut dysbiosis and psychological stress could contribute to the development of novel therapeutic strategies to improve SCI patients’ quality of life.
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Piras C, Pintus BM, Noto A, Evangelista M, Fanos V, Musu M, Mussap M, Atzori L, Sardo S, Finco G. Metabolomics and Microbiomics: New Potential Strategies in Chronic Pain Syndrome. J Pain Res 2022; 15:723-731. [PMID: 35310896 PMCID: PMC8923834 DOI: 10.2147/jpr.s354516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 03/02/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Cristina Piras
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042, Italy
| | - Bruno Maria Pintus
- Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, 09042, Italy
| | - Antonio Noto
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042, Italy
- Correspondence: Antonio Noto, Email
| | - Maurizio Evangelista
- Department of Anesthesiology and Pain Medicine, Cattolica University, Rome, 00168, Italy
| | - Vassilios Fanos
- Department of Surgical Science, University of Cagliari, Monserrato, 09042, Italy
| | - Mario Musu
- Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, 09042, Italy
| | - Michele Mussap
- Department of Surgical Science, University of Cagliari, Monserrato, 09042, Italy
| | - Luigi Atzori
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042, Italy
| | - Salvatore Sardo
- Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, 09042, Italy
| | - Gabriele Finco
- Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, 09042, Italy
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Herrera-Rincon C, Murciano-Brea J, Geuna S. Can we promote neural regeneration through microbiota-targeted strategies? Introducing the new concept of neurobiotics. Neural Regen Res 2022; 17:1965-1966. [PMID: 35142677 PMCID: PMC8848601 DOI: 10.4103/1673-5374.335149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Celia Herrera-Rincon
- Department of Biodiversity, Ecology & Evolution, and Modeling, Data Analysis & Computational Tools for Biology Research Group, Biomathematics Unit, Complutense University of Madrid, Madrid, Spain
| | - Julia Murciano-Brea
- Department of Biodiversity, Ecology & Evolution, and Modeling, Data Analysis & Computational Tools for Biology Research Group, Biomathematics Unit, Complutense University of Madrid, Madrid, Spain
| | - Stefano Geuna
- Department of Clinical and Biological Sciences, and Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Turin, Italy
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Shen CL, Wang R, Ji G, Elmassry MM, Zabet-Moghaddam M, Vellers H, Hamood AN, Gong X, Mirzaei P, Sang S, Neugebauer V. Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation. J Nutr Biochem 2022; 100:108904. [PMID: 34748918 PMCID: PMC8794052 DOI: 10.1016/j.jnutbio.2021.108904] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 09/24/2021] [Accepted: 10/08/2021] [Indexed: 02/03/2023]
Abstract
Neuroinflammation is a central factor in neuropathic pain (NP). Ginger is a promising bioactive compound in NP management due to its anti-inflammatory property. Emerging evidence suggests that gut microbiome and gut-derived metabolites play a key role in NP. We evaluated the effects of two ginger root extracts rich in gingerols (GEG) and shogaols (SEG) on pain sensitivity, anxiety-like behaviors, circulating cell-free mitochondrial DNA (ccf-mtDNA), gut microbiome composition, and fecal metabolites in rats with NP. Sixteen male rats were divided into four groups: sham, spinal nerve ligation (SNL), SNL+0.75%GEG in diet, and SNL+0.75%SEG in diet groups for 30 days. Compared to SNL group, both SNL+GEG and SNL+SEG groups showed a significant reduction in pain- and anxiety-like behaviors, and ccf-mtDNA level. Relative to the SNL group, both SNL+GEG and SNL+SEG groups increased the relative abundance of Lactococcus, Sellimonas, Blautia, Erysipelatoclostridiaceae, and Anaerovoracaceae, but decreased that of Prevotellaceae UCG-001, Rikenellaceae RC9 gut group, Mucispirillum and Desulfovibrio, Desulfovibrio, Anaerofilum, Eubacterium siraeum group, RF39, UCG-005, Lachnospiraceae NK4A136 group, Acetatifactor, Eubacterium ruminantium group, Clostridia UCG-014, and an uncultured Anaerovoracaceae. GEG and SEG had differential effects on gut-derived metabolites. Compared to SNL group, SNL+GEG group had higher level of 1'-acetoxychavicol acetate, (4E)-1,7-Bis(4-hydroxyphenyl)-4-hepten-3-one, NP-000629, 7,8-Dimethoxy-3-(2-methyl-3-buten-2-yl)-2H-chromen-2-one, 3-{[4-(2-Pyrimidinyl)piperazino]carbonyl}-2-pyrazinecarboxylic acid, 920863, and (1R,3R,7R,13S)-13-Methyl-6-methylene-4,14,16-trioxatetracyclo[11.2.1.0∼1,10∼.0∼3,7∼]hexadec-9-en-5-one, while SNL+SEG group had higher level for (±)-5-[(tert-Butylamino)-2'-hydroxypropoxy]-1_2_3_4-tetrahydro-1-naphthol and dehydroepiandrosteronesulfate. In conclusion, ginger is a promising functional food in the management of NP, and further investigations are necessary to assess the role of ginger on gut-brain axis in pain management.
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Affiliation(s)
- Chwan-Li Shen
- Department of Pathology, Texas Technical University Health Sciences Center, Lubbock, Texas; Center of Excellence for Integrative Health, Texas Technical University Health Sciences Center, Lubbock, Texas; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Technical University Health Sciences Center, Lubbock, Texas.
| | - Rui Wang
- Department of Pathology, Texas Technical University Health Sciences Center, Lubbock, Texas
| | - Guangchen Ji
- Department of Pharmacology and Neuroscience, Texas Technical University Health Sciences Center, Lubbock, Texas
| | - Moamen M Elmassry
- Department of Biological Sciences, Texas Technical University, Lubbock, Texas
| | | | - Heather Vellers
- Department of Kinesiology and Sport Management, Texas Technical University, Lubbock, Texas
| | - Abdul N Hamood
- Department of Immunology and Molecular Microbiology, Texas Technical University Health Sciences Center, Lubbock, Texas; Department of Surgery, Texas Technical University Health Sciences Center, Lubbock, Teaxs
| | - Xiaoxia Gong
- Center for Biotechnology and Genomics, Texas Technical University, Lubbock, Texas
| | - Parvin Mirzaei
- Center for Biotechnology and Genomics, Texas Technical University, Lubbock, Texas
| | - Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post Harvest Technologies, North Carolina A&T State University, North Carolina Research Campus, Kannapolis, North Carolina
| | - Volker Neugebauer
- Center of Excellence for Integrative Health, Texas Technical University Health Sciences Center, Lubbock, Texas; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Technical University Health Sciences Center, Lubbock, Texas; Department of Pharmacology and Neuroscience, Texas Technical University Health Sciences Center, Lubbock, Texas
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Alostaz H, Cai L. Biomarkers from Secondary Complications in Spinal Cord Injury. CURRENT PHARMACOLOGY REPORTS 2022; 8:20-30. [PMID: 36147780 PMCID: PMC9491488 DOI: 10.1007/s40495-021-00268-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/29/2023]
Abstract
PURPOSE OF REVIEW In the USA, spinal cord injury (SCI) occurs in 40 people per million every year due to events such as car accidents, falls, violence, or sports injury. Secondary complications that arise from SCI are life-threatening and should be treated as early as possible. In some cases, it is not completely obvious what complication a patient may have until it is too late. Therefore, biomarkers are required to assess the levels of secondary complications after SCI. As there are several complications that pose different warning signs, different biomarkers may be beneficial in early detection, maintenance, and long-term care for patients with SCI. RECENT FINDINGS Numerous studies have been conducted on biomarkers in various SCI and its related complications, such as neuropathic pain and deep vein thrombosis. In recent years, research has expanded with biomarkers discovered by cellular and molecular, genome-wide transcriptomic analysis, bioinformatics, and clinical studies. Biomarkers have allowed early prediction of the severity of secondary complications due to SCI. SUMMARY In this review, we summarize recent studies on the common biomarkers for the secondary complications related to SCI. We highlight the reliable biomarkers that have been tested, e.g., sclerostin, NGF, D-dimer, oncostatin M (OSM), microbiota, and C-reactive protein, which are valuable and with clinical importance. This review also emphasizes continuing research in biomarkers as they can provide valuable cellular and molecular insight into secondary complications after SCI.
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Affiliation(s)
- Hani Alostaz
- Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA
| | - Li Cai
- Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA
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Yuan B, Lu XJ, Wu Q. Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention. Front Immunol 2022; 12:800796. [PMID: 35003127 PMCID: PMC8740048 DOI: 10.3389/fimmu.2021.800796] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 12/09/2021] [Indexed: 12/15/2022] Open
Abstract
Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.
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Affiliation(s)
- Bin Yuan
- Department of Neurosurgery, The Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China
| | - Xiao-Jie Lu
- Department of Neurosurgery, The Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.,Department of Neurosurgery, The Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Qi Wu
- Department of Neurosurgery, Jinling Hospital, Nanjing University, School of Medicine, Nanjing, China
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Kiryachkov YY, Bosenko SA, Muslimov BG, Petrova MV. Dysfunction of the Autonomic Nervous System and its Role in the Pathogenesis of Septic Critical Illness (Review). Sovrem Tekhnologii Med 2021; 12:106-116. [PMID: 34795998 PMCID: PMC8596275 DOI: 10.17691/stm2020.12.4.12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Indexed: 12/05/2022] Open
Abstract
Dysfunction of the autonomic nervous system (ANS) of the brain in sepsis can cause severe systemic inflammation and even death. Numerous data confirmed the role of ANS dysfunction in the occurrence, course, and outcome of systemic sepsis. The parasympathetic part of the ANS modifies the inflammation through cholinergic receptors of internal organs, macrophages, and lymphocytes (the cholinergic anti-inflammatory pathway). The sympathetic part of ANS controls the activity of macrophages and lymphocytes by influencing β2-adrenergic receptors, causing the activation of intracellular genes encoding the synthesis of cytokines (anti-inflammatory beta2-adrenergic receptor interleukin-10 pathway, β2AR–IL-10). The interaction of ANS with infectious agents and the immune system ensures the maintenance of homeostasis or the appearance of a critical generalized infection. During inflammation, the ANS participates in the inflammatory response by releasing sympathetic or parasympathetic neurotransmitters and neuropeptides. It is extremely important to determine the functional state of the ANS in critical conditions, since both cholinergic and sympathomimetic agents can act as either anti- or pro-inflammatory stimuli.
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Affiliation(s)
- Y Y Kiryachkov
- Head of the Department of Surgical and Resuscitation Technologies; Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25, Bldg 2, Petrovka St., Moscow, 107031, Russia
| | - S A Bosenko
- Anesthesiologist; Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25, Bldg 2, Petrovka St., Moscow, 107031, Russia
| | - B G Muslimov
- Deputy Chief Physician for Anesthesiology and Intensive Care; Konchalovsky Central City Hospital, 2, Bldg 1, Kashtanovaya Alley, Zelenograd, Moscow, 124489, Russia
| | - M V Petrova
- Professor, Deputy Director Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25, Bldg 2, Petrovka St., Moscow, 107031, Russia
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Cheng J, Li W, Wang Y, Cao Q, Ni Y, Zhang W, Guo J, Chen B, Zang Y, Zhu Y. Electroacupuncture modulates the intestinal microecology to improve intestinal motility in spinal cord injury rats. Microb Biotechnol 2021; 15:862-873. [PMID: 34797954 PMCID: PMC8913878 DOI: 10.1111/1751-7915.13968] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 10/29/2021] [Accepted: 10/30/2021] [Indexed: 12/14/2022] Open
Abstract
Spinal cord injury (SCI) is a disease involving gastrointestinal disorders. The underlying mechanisms of the potential protective effects of electroacupuncture (EA) and 5-hydroxytryptamine (5-HT) system on SCI remain unknown. We investigated whether EA improves gut microbial dysbiosis in SCI and regulates the 5-HT system. 16S rDNA gene sequencing was applied to investigate alterations in the gut microbiome of the rats. Faecal metabolites and the expression of the 5-HT system were detected. EA and faecal microbiota transplantation (FMT) treatment facilitated intestinal transmission functional recovery and restored the colon morphology of SCI rats. The composition of the intestinal microbiota, including numbers of phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea, were amplified in SCI rats, and EA and FMT significantly reshaped the intestinal microbiota. SCI resulted in disturbed metabolic conditions in rats, and the EA and FMT group showed increased amounts of catechin compared with SCI rats. SCI inhibited 5-HT system expression in the colon, which was significantly reversed by EA and FMT treatment. Therefore, EA may ameliorate SCI by modulating microbiota and metabolites and regulate the 5-HT system. Our study provides new insights into the pathogenesis and therapy of SCI from the perspective of microbiota and 5-HT regulation.
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Affiliation(s)
- Jie Cheng
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Weimin Li
- The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Ying Wang
- The Ninth People's Hospital of Wuxi affiliated to Soochow University, Wuxi, China.,Department of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Qing Cao
- Department of Kinesiology, Shanghai University of Sport, Shanghai, China.,Zigong Forth People's Hospital, Zigong, China
| | - Ying Ni
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Wenyi Zhang
- Zhongshan Rehabilitation Hospital Affiliated to Jiangsu Provincial People's Hospital, Nanjing, China
| | - Jiabao Guo
- The Second Clinical Medical School, Xuzhou Medical University, Xuzhou, China
| | - Binglin Chen
- The Second Clinical Medical School, Xuzhou Medical University, Xuzhou, China
| | - Yaning Zang
- Department of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Yi Zhu
- The Second Affiliated Hospital of Hainan Medical University, Haikou, China.,The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Doelman A, Tigchelaar S, McConeghy B, Sinha S, Keung MS, Manouchehri N, Webster M, Fisk S, Morrison C, Streijger F, Nislow C, Kwon BK. Characterization of the gut microbiome in a porcine model of thoracic spinal cord injury. BMC Genomics 2021; 22:775. [PMID: 34717545 PMCID: PMC8557039 DOI: 10.1186/s12864-021-07979-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 09/01/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The gut microbiome is a diverse network of bacteria which inhabit our digestive tract and is crucial for efficient cellular metabolism, nutrient absorption, and immune system development. Spinal cord injury (SCI) disrupts autonomic function below the level of injury and can alter the composition of the gut microbiome. Studies in rodent models have shown that SCI-induced bacterial imbalances in the gut can exacerbate the spinal cord damage and impair recovery. In this study we, for the first time, characterized the composition of the gut microbiome in a Yucatan minipig SCI model. We compared the relative abundance of the most dominant bacterial phyla in control samples to those collected from animals who underwent a contusion-compression SCI at the 2nd or 10th Thoracic level. RESULTS We identify specific bacterial fluctuations that are unique to SCI animals, which were not found in uninjured animals given the same dietary regimen or antibiotic administration. Further, we identified a specific time-frame, "SCI-acute stage", during which many of these bacterial fluctuations occur before returning to "baseline" levels. CONCLUSION This work presents a dynamic view of the microbiome changes that accompany SCI, establishes a resource for future studies and to understand the changes that occur to gut microbiota after spinal cord injury and may point to a potential therapeutic target for future treatment.
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Affiliation(s)
- Adam Doelman
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC Canada
| | - Seth Tigchelaar
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC Canada
| | - Brian McConeghy
- Sequencing and Bioinformatics Consortium, University of British Columbia, Vancouver, BC Canada
| | - Sunita Sinha
- Sequencing and Bioinformatics Consortium, University of British Columbia, Vancouver, BC Canada
| | - Martin S. Keung
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC Canada
| | - Neda Manouchehri
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC Canada
| | - Megan Webster
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC Canada
| | - Shera Fisk
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC Canada
| | - Charlotte Morrison
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC Canada
| | - Femke Streijger
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC Canada
| | - Corey Nislow
- Sequencing and Bioinformatics Consortium, University of British Columbia, Vancouver, BC Canada
| | - Brian K. Kwon
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC Canada
- Department of Orthopedics, Vancouver Spine Surgery Institute, University of British Columbia, Vancouver, BC Canada
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Rong Z, Huang Y, Cai H, Chen M, Wang H, Liu G, Zhang Z, Wu J. Gut Microbiota Disorders Promote Inflammation and Aggravate Spinal Cord Injury Through the TLR4/MyD88 Signaling Pathway. Front Nutr 2021; 8:702659. [PMID: 34589510 PMCID: PMC8473614 DOI: 10.3389/fnut.2021.702659] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 08/23/2021] [Indexed: 12/02/2022] Open
Abstract
Background: In spinal cord injury (SCI), systemic inflammation and the death of nerve cells in the spinal cord are life threatening. The connection between gut microbiota and signaling pathways has been a hot research topic in recent years. The Toll-like receptor 4/Myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway is closely related to the inflammatory response. This study explored whether the gut microbiota imbalance could affect the TLR4/MyD88 signaling pathway to regulate SCI to provide a new basis for SCI research and treatment. Methods: An SCI model was constructed to study the influence on the injury of gut microbiota. 16S amplicon sequencing was used to identify the diversity and abundance of gut microbes. Fecal microbiota transplantation was performed in mice with SCI. ELISA was used to detect the serum levels of pro-inflammatory and anti-inflammatory factors in mice. Hematoxylin and eosin staining was used to observe SCI in mice. Immunofluorescence was used to detect the rates of loss glial fibrillary acidic protein (GFAP), neuronal nuclear protein (NeuN), and ionized calcium-binding adapter molecule 1 (IBA1) in the spinal cord as indicators of apoptosis. The expression of the TLR4/MyD88 signaling pathway was detected by qRT-PCR and western blotting. Results: Significant differences were observed in the gut microbiota of SCI mice and normal mice. The gut microbiota of SCI mice was imbalanced. The levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in SCI mice were increased, as was the level of the toxic induced nitric oxide synthase. The levels of anti-inflammatory factors IL-4, transforming growth factor-β, and IL-10 were decreased, as was the level of arginase-1. The apoptosis rates of GFAP, NeuN, and IBA1 were increased. The TLR4/MyD88 signaling pathway was activated. In the SCI group, inflammation increased after fecal transplantation, apoptosis of GFAP, NeuN, and IBA1 increased, and SCI was more serious. Conclusion: The TLR4/MyD88 signaling pathway promotes the death of nerve cells by inducing inflammation. Gut microbiota dysregulation can lead to aggravated SCI by activating the TLR4/MyD88 signaling pathway.
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Affiliation(s)
- Zijie Rong
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China.,Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
| | - Yuliang Huang
- Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China.,Department of Orthopaedics, Huizhou Municipal Central Hospital, Huizhou, China
| | - Honghua Cai
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China.,Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
| | - Min Chen
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China.,Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
| | - Hao Wang
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China.,Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
| | - Guihua Liu
- Department of Spine Surgery, Huizhou Municipal Central Hospital, Huizhou, China.,Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China
| | - Zhiwen Zhang
- Orthopaedic Institute, Huizhou Municipal Central Hospital, Huizhou, China.,Department of Orthopaedics, Huizhou Municipal Central Hospital, Huizhou, China
| | - Jiawen Wu
- Department of Spine Surgery, The People's Hospital of Longhua, Shenzhen Longhua Clinical Medical College of Guangdong Medical University, Shenzhen, China
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Spinal cord injury in mice impacts central and peripheral pathology in a severity-dependent manner. Pain 2021; 163:1172-1185. [PMID: 34490852 DOI: 10.1097/j.pain.0000000000002471] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 08/25/2021] [Indexed: 11/26/2022]
Abstract
ABSTRACT Chronic pain is a common medical complication experienced by those living with spinal cord injury (SCI) and leads to worsened quality of life. The pathophysiology of SCI pain is poorly understood, hampering the development of safe and efficacious therapeutics. We therefore sought to develop a clinically relevant model of SCI with a strong pain phenotype and characterize the central and peripheral pathology after injury. A contusion (50 kdyn) injury, with and without sustained compression (60 seconds) of the spinal cord, was carried out on female C57BL/6J mice. Mice with compression of the spinal cord exhibited significantly greater heat and mechanical hypersensitivity starting at 7 days post-injury, concomitant with reduced locomotor function, compared to those without compression. Immunohistochemical analysis of spinal cord tissue revealed significantly less myelin sparing and increased macrophage activation in mice with compression compared to those without. As measured by flow cytometry, immune cell infiltration and activation were significantly greater in the spinal cord (phagocytic myeloid cells and microglia) and dorsal root ganglia (Ly6C+ monocytes) following compression injury. We also decided to investigate the gastrointestinal microbiome, as it has been shown to be altered in SCI patients and has recently been shown to play a role in immune system maturation and pain. We found increased dysbiosis of the gastrointestinal microbiome in an injury severity-dependent manner. The use of this contusion-compression model of SCI may help advance the preclinical assessment of acute and chronic SCI pain and lead to a better understanding of mechanisms contributing to this pain.
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Goodus MT, Carson KE, Sauerbeck AD, Dey P, Alfredo AN, Popovich PG, Bruno RS, McTigue DM. Liver inflammation at the time of spinal cord injury enhances intraspinal pathology, liver injury, metabolic syndrome and locomotor deficits. Exp Neurol 2021; 342:113725. [PMID: 33933462 PMCID: PMC8784048 DOI: 10.1016/j.expneurol.2021.113725] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 04/08/2021] [Accepted: 04/22/2021] [Indexed: 02/07/2023]
Abstract
The current high obesity rates mean that neurological injuries are increasingly sustained on a background of systemic pathology, including liver inflammation, which likely has a negative impact on outcomes. Because obesity involves complex pathology, the effect of hepatic inflammation alone on neurological recovery is unknown. Thus, here we used a gain-of-function model to test if liver inflammation worsens outcome from spinal cord injury (SCI) in rats. Results show liver inflammation concomitant with SCI exacerbated intraspinal pathology and impaired locomotor recovery. Hepatic inflammation also potentiated SCI-induced non-alcoholic steatohepatitis (NASH), endotoxemia and insulin resistance. Circulating and cerebrospinal levels of the liver-derived protein Fetuin-A were higher in SCI rats with liver inflammation, and, when microinjected into intact spinal cords, Fetuin-A caused macrophage activation and neuron loss. Thus, liver inflammation functions as a disease modifying factor to impair recovery from SCI, and Fetuin-A is a potential neuropathological mediator. Since SCI alone induces acute liver inflammation, the liver may be a novel clinical target for improving recovery from SCI.
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Affiliation(s)
- Matthew T Goodus
- The Belford Center for Spinal Cord Injury, Ohio State University, Columbus, OH, USA; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, USA
| | - Kaitlin E Carson
- The Belford Center for Spinal Cord Injury, Ohio State University, Columbus, OH, USA; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, USA
| | - Andrew D Sauerbeck
- The Belford Center for Spinal Cord Injury, Ohio State University, Columbus, OH, USA; Department of Neurology, Washington University in St. Louis, Missouri, USA
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India
| | - Anthony N Alfredo
- The Belford Center for Spinal Cord Injury, Ohio State University, Columbus, OH, USA; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, USA
| | - Phillip G Popovich
- The Belford Center for Spinal Cord Injury, Ohio State University, Columbus, OH, USA; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, USA
| | - Richard S Bruno
- Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH, USA
| | - Dana M McTigue
- The Belford Center for Spinal Cord Injury, Ohio State University, Columbus, OH, USA; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, USA.
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Yu B, Qiu H, Cheng S, Ye F, Li J, Chen S, Zhou L, Yang Y, Zhong C, Li J. Profile of gut microbiota in patients with traumatic thoracic spinal cord injury and its clinical implications: a case-control study in a rehabilitation setting. Bioengineered 2021; 12:4489-4499. [PMID: 34311653 PMCID: PMC8806552 DOI: 10.1080/21655979.2021.1955543] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Gut microbiota are the candidate biomarkers for neurogenic bowel dysfunction (NBD) in patients with spinal cord injury (SCI). We aimed to identify the common features between patients with varying degree of thoracic SCI and healthy individuals and subpopulations of microbiota correlated with the serum biomarkers. Twenty-one patients with complete thoracic SCI (CTSCI), 24 with incomplete thoracic SCI (ITSCI), and 24 healthy individuals (HC) were enrolled in this study. Fresh stool samples and clinical data were collected from all participants, and their bowel functions with SCI were assessed. Microbial diversity and composition were analyzed by sequencing the 16S rRNA gene. The features of gut microbiota correlated with the serum biomarkers and their functions were investigated. The mean NBD score of patients with CTSCI was higher than that of patients with ITSCI. Diversity of the gut microbiota in SCI group was reduced, and with an increase in the degree of damage, alpha diversity had decreased gradually. The composition of gut microbiota in patients with SCI was distinct from that in healthy individuals, and CTSCI group exhibited further deviation than ITSCI group compared to healthy individuals. Four serum biomarkers were found to be correlated with most differential genera. Patients with thoracic SCI present gut dysbiosis, which is more pronounced in patients with CTSCI than in those with ITSCI. Therefore, the gut microbiota profile may serve as the signatures for bowel and motor functions in patients with thoracic SCI.
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Affiliation(s)
- Binbin Yu
- Center of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,School of Rehabilitation Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Huaide Qiu
- Center of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,School of Rehabilitation Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Shupeng Cheng
- Center of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,School of Rehabilitation Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Feng Ye
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University
| | - Jiahui Li
- Center of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Sijing Chen
- Center of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Li Zhou
- Center of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yumei Yang
- Spinal Cord Injury Ward, Jiangsu Zhongshan Geriatric Rehabilitation Hospital, Nanjing, China
| | - Caiyun Zhong
- School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Jianan Li
- Center of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,School of Rehabilitation Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China
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McCoubrey LE, Elbadawi M, Orlu M, Gaisford S, Basit AW. Machine Learning Uncovers Adverse Drug Effects on Intestinal Bacteria. Pharmaceutics 2021; 13:1026. [PMID: 34371718 PMCID: PMC8308984 DOI: 10.3390/pharmaceutics13071026] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 06/24/2021] [Accepted: 06/30/2021] [Indexed: 02/07/2023] Open
Abstract
The human gut microbiome, composed of trillions of microorganisms, plays an essential role in human health. Many factors shape gut microbiome composition over the life span, including changes to diet, lifestyle, and medication use. Though not routinely tested during drug development, drugs can exert profound effects on the gut microbiome, potentially altering its functions and promoting disease. This study develops a machine learning (ML) model to predict whether drugs will impair the growth of 40 gut bacterial strains. Trained on over 18,600 drug-bacteria interactions, 13 distinct ML models are built and compared, including tree-based, ensemble, and artificial neural network techniques. Following hyperparameter tuning and multi-metric evaluation, a lead ML model is selected: a tuned extra trees algorithm with performances of AUROC: 0.857 (±0.014), recall: 0.587 (±0.063), precision: 0.800 (±0.053), and f1: 0.666 (±0.042). This model can be used by the pharmaceutical industry during drug development and could even be adapted for use in clinical settings.
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Affiliation(s)
| | | | | | | | - Abdul W. Basit
- UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; (L.E.M.); (M.E.); (M.O.); (S.G.)
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Carbohydrate Considerations for Athletes with a Spinal Cord Injury. Nutrients 2021; 13:nu13072177. [PMID: 34202761 PMCID: PMC8308372 DOI: 10.3390/nu13072177] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/10/2021] [Accepted: 06/21/2021] [Indexed: 12/20/2022] Open
Abstract
The Paralympic movement is growing in popularity, resulting in increased numbers of athletes with a spinal cord injury (SCI) competing in various sport disciplines. Athletes with an SCI require specialized recommendations to promote health and to maximize performance, as evidenced by their metabolic and physiological adaptations. Nutrition is a key factor for optimal performance; however, scientifically supported nutritional recommendations are limited. This review summarizes the current knowledge regarding the importance of carbohydrates (CHO) for health and performance in athletes with an SCI. Factors possibly affecting CHO needs, such as muscle atrophy, reduced energy expenditure, and secondary complications are analyzed comprehensively. Furthermore, a model calculation for CHO requirements during an endurance event is provided. Along with assessing the effectiveness of CHO supplementation in the athletic population with SCI, the evaluation of their CHO intake from the available research supplies background to current practices. Finally, future directions are identified. In conclusion, the direct transfer of CHO guidelines from able-bodied (AB) athletes to athletes with an SCI does not seem to be reasonable. Based on the critical role of CHOs in exercise performance, establishing recommendations for athletes with an SCI should be the overall objective for prospective research.
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